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...

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

DTIC Science & Technology

1986-04-29

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

CMS results in the Combined Computing Readiness Challenge CCRC'08

NASA Astrophysics Data System (ADS)

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

2009-12-01

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

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...

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.

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

PubMed

Çelik, Derya

2016-01-01

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

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.

Gender differences in CMS and the effects of antidepressant venlafaxine in rats.

PubMed

Xing, Yanli; He, Jie; Hou, Jian; Lin, Fei; Tian, Jingwei; Kurihara, Hiroshi

2013-11-01

Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cavernous malformations of the brainstem: three-dimensional-constructive interference in steady-state magnetic resonance imaging for improvement of surgical approach and clinical results.

PubMed

Zausinger, Stefan; Yousry, Indra; Brueckmann, Hartmut; Schmid-Elsaesser, Robert; Tonn, Joerg-Christian

2006-02-01

The indications for resection of cavernous malformations (CMs) of the brainstem include neurological deficits, (recurrent) hemorrhage, and surgically accessible location. In particular, knowledge of the thickness of the parenchymal layer and of the CM's spatial relation to nuclei, tracts, cranial nerves, and vessels is critical for planning the surgical approach. We reviewed the operative treatment of 13 patients with 14 brainstem CMs, with special regard to refined three-dimensional (3D)-constructive interference in steady-state (CISS) magnetic resonance imaging (MRI). Patients were evaluated neurologically and by conventional spin-echo/fast spin-echo and 3D-CISS MRI. Surgery was performed with the use of microsurgical techniques and neurophysiological monitoring. Eleven CMs were located in the pons/pontomedullary region; 10 of the 11 were operated on via the lateral suboccipital approach. Three CMs were located near the floor of the fourth ventricle and operated on via the median suboccipital approach, with total removal of all CMs. Results were excellent or good in 10 patients; one patient transiently required tracheostomy, and two patients developed new hemipareses/ataxia with subsequent improvement. Not only did 3D-CISS sequences allow improved judgment of the thickness of the parenchymal layer over the lesion compared with spin-echo/fast spin-echo MRI, but 3D-CISS imaging also proved particularly superior in demonstrating the spatial relation of the lesion to fairly "safe" entry zones (e.g., between the trigeminal nerve and the VIIth and VIIIth nerve groups) by displaying the cranial nerves and vessels within the cerebellopontine cistern more precisely. Surgical treatment of brainstem CMs is recommended in symptomatic patients. Especially in patients with lesions situated ventrolaterally, the 3D-CISS sequence seems to be a valuable method for identifying the CM's relation to safe entry zones, thereby facilitating the surgical approach.

Alignment of the CMS Tracker: Latest Results from LHC Run-II

NASA Astrophysics Data System (ADS)

Mittag, Gregor; CMS Collaboration

2017-10-01

The all-silicon design of the tracking system of the CMS experiment provides excellent measurements of charged-particle tracks and an efficient tagging of jets. Conditions of the CMS tracker changed repeatedly during the 2015/2016 shutdown and the 2016 data-taking period. Still the true position and orientation of each of the 15 148 silicon strip and 1440 silicon pixel modules need to be known with high precision for all intervals. The alignment constants also need to be promptly re-adjusted each time the state of the CMS magnet is changed between 0T and 3.8 T. Latest Run-II results of the CMS tracker alignment and resolution performance are presented, which are obtained using several millions of reconstructed tracks from collision and cosmic-ray data of 2016. The geometries and the resulting performance of physics observables are carefully validated. In addition to the offline alignment, an online procedure has been put in place which continuously monitors movements of the pixel high-level structures and triggers updates of the alignment constants if certain thresholds are exceeded.

Particle-flow reconstruction and global event description with the CMS detector

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.; Suarez Gonzalez, J.; 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.; Abu Zeid, S.; 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.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; 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.; 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.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; 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.; Da Silveira, G. G.; Damiao, D. De Jesus; 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.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. 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.; 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.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M., Jr.; Carrera Jarrin, E.; 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.; Hamel de Monchenault, G.; 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.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Miné, P.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; 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.; Carrillo Montoya, C. A.; 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.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Cherepanov, V.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Anuar, A. A. Bin; Borras, K.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Dolinska, G.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Karacheban, O.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Sahin, M. Ö.; Saxena, P.; Schoerner-Sadenius, T.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wissing, C.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hoffmann, M.; Junkes, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Baus, C.; Berger, J.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Fink, S.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Goldenzweig, P.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Katkov, I.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Röcker, S.; Roscher, F.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; 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.; 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.; Pasztor, G.; Bencze, G.; Hajdu, C.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Komaragiri, J. R.; Bahinipati, S.; Bhowmik, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Bhawandeep, U.; Chawla, R.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Kumari, P.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Sharma, V.; Bhattacharya, R.; Bhattacharya, S.; Chatterjee, K.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy, D.; Chowdhury, S. Roy; Sarkar, S.; Sharan, M.; Thakur, S.; Behera, P. K.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Netrakanti, P. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Dugad, S.; Kole, G.; Mahakud, B.; Mitra, S.; Mohanty, G. B.; Parida, B.; Sur, N.; Sutar, B.; Banerjee, S.; Dewanjee, R. K.; Ganguly, S.; Guchait, M.; Jain, Sa.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Sarkar, T.; Wickramage, N.; Chauhan, S.; Dube, S.; Hegde, V.; Kapoor, A.; Kothekar, K.; Pandey, S.; Rane, A.; Sharma, S.; Chenarani, S.; Eskandari Tadavani, E.; Etesami, S. M.; Khakzad, M.; Najafabadi, M. Mohammadi; 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.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; 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.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Trauger, H.; 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.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Tapia Takaki, J. D.; 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.; Gomez Ceballos, G.; 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.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Malta Rodrigues, A.; 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.; Teixeira De Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; 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.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; 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.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; 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.; 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.; Zaleski, S.; Belknap, D. A.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

2017-10-01

The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMS performance for jet and hadronic τ decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. The data collected by CMS at a centre-of-mass energy of 8\\TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.

Charge-dependent azimuthal correlations in pPb collisions with CMS experiment

NASA Astrophysics Data System (ADS)

Tu, Zhoudunming; CMS Collaboration

2017-11-01

Charge-dependent azimuthal correlations relative to the event plane in AA collisions have been suggested as providing evidence for the chiral magnetic effect (CME) caused by local strong parity violation. However, the observation of the CME remains inconclusive because of several possible sources of background correlations that may account for part or all of the observed signals. This talk will present the first application of three-particle, charge-dependent azimuthal correlation analysis in proton-nucleus collisions, using pPb data collected with the CMS experiment at the LHC at √{sNN} = 5.02 TeV. The differences found in comparing same and opposite sign correlations are studied as a function of event multiplicity and the pseudorapidity gap between two of the particles detected in the CMS tracker detector. After selecting events with comparable charge-particle multiplicities, the results for pPb collisions are found to be similar to those for PbPb collisions collected at the same collision energy. With a reduced magnetic field strength and a random field orientation in high multiplicity pPb events, the CME contribution to any charge separation signal is expected to be much smaller than found in peripheral PbPb events. These results pose a challenge for the interpretation of charge-dependent azimuthal correlations in heavy ion collisions in terms of the chiral magnetic effect.

A low temperature co-fired ceramic power inductor manufactured using a glass-free ternary composite material system

NASA Astrophysics Data System (ADS)

Li, Yuanxun; Xie, Yunsong; Xie, Ru; Chen, Daming; Han, Likun; Su, Hua

2018-03-01

A glass-free ternary composite material system (CMS) manufactured employing the low temperature ( 890 ° C ) co-fired ceramic (LTCC) technique is reported. This ternary CMS consists of silver, NiCuZn ferrite, and Zn2SiO4 ceramic. The reported device fabricated from this ternary CMS is a power inductor with a nominal inductance of 1.0 μH. Three major highlights were achieved from the device and the material study. First, unlike most other LTCC methods, no glass is required to be added in either of the dielectric materials in order to co-fire the NiCuZn ferrite, Zn2SiO4 ceramic, and silver. Second, a successfully co-fired silver, NiCuZn, and Zn2SiO4 device can be achieved by optimizing the thermal shrinkage properties of both NiCuZn and Zn2SiO4, so that they have a very similar temperature shrinkage profile. We have also found that strong non-magnetic elemental diffusion occurs during the densification process, which further enhances the success rate of manufacturing co-fired devices. Last but not least, elemental mapping suggests that strong magnetic elemental diffusion between NiCuZn and Zn2SiO4 has been suppressed during the co-firing process. The investigation of electrical performance illustrates that while the ordinary binary CMS based power inductor can deal with 400 mA DC, the ternary CMS based power inductor is able to handle higher DC currents, 700 mA and 620 mA DC, according to both simulation and experiment demonstrations, respectively.

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.

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.

The CMS experiment at the CERN LHC

NASA Astrophysics Data System (ADS)

CMS Collaboration; Chatrchyan, S.; Hmayakyan, G.; Khachatryan, V.; Sirunyan, A. M.; Adam, W.; Bauer, T.; Bergauer, T.; Bergauer, H.; Dragicevic, M.; Erö, J.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Glaser, P.; Hartl, C.; Hoermann, N.; Hrubec, J.; Hänsel, S.; Jeitler, M.; Kastner, K.; Krammer, M.; Magrans de Abril, I.; Markytan, M.; Mikulec, I.; Neuherz, B.; Nöbauer, T.; Oberegger, M.; Padrta, M.; Pernicka, M.; Porth, P.; Rohringer, H.; Schmid, S.; Schreiner, T.; Stark, R.; Steininger, H.; Strauss, J.; Taurok, A.; Uhl, D.; Waltenberger, W.; Walzel, G.; Widl, E.; Wulz, C.-E.; Petrov, V.; Prosolovich, V.; Chekhovsky, V.; Dvornikov, O.; Emeliantchik, I.; Litomin, A.; Makarenko, V.; Marfin, I.; Mossolov, V.; Shumeiko, N.; Solin, A.; Stefanovitch, R.; Suarez Gonzalez, J.; Tikhonov, A.; Fedorov, A.; Korzhik, M.; Missevitch, O.; Zuyeuski, R.; Beaumont, W.; Cardaci, M.; DeLanghe, E.; DeWolf, E. A.; Delmeire, E.; Ochesanu, S.; Tasevsky, M.; Van Mechelen, P.; D'Hondt, J.; DeWeirdt, S.; Devroede, O.; Goorens, R.; Hannaert, S.; Heyninck, J.; Maes, J.; Mozer, M. U.; Tavernier, S.; Van Doninck, W.; Van Lancker, L.; Van Mulders, P.; Villella, I.; Wastiels, C.; Yu, C.; Bouhali, O.; Charaf, O.; Clerbaux, B.; DeHarenne, P.; DeLentdecker, G.; Dewulf, J. P.; Elgammal, S.; Gindroz, R.; Hammad, G. H.; Mahmoud, T.; Neukermans, L.; Pins, M.; Pins, R.; Rugovac, S.; Stefanescu, J.; Sundararajan, V.; Vander Velde, C.; Vanlaer, P.; Wickens, J.; Tytgat, M.; Assouak, S.; Bonnet, J. L.; Bruno, G.; Caudron, J.; DeCallatay, B.; DeFavereau DeJeneret, J.; DeVisscher, S.; Demin, P.; Favart, D.; Felix, C.; Florins, B.; Forton, E.; Giammanco, A.; Grégoire, G.; Jonckman, M.; Kcira, D.; Keutgen, T.; Lemaitre, V.; Michotte, D.; Militaru, O.; Ovyn, S.; Pierzchala, T.; Piotrzkowski, K.; Roberfroid, V.; Rouby, X.; Schul, N.; Van der Aa, O.; Beliy, N.; Daubie, E.; Herquet, P.; Alves, G.; Pol, M. E.; Souza, M. H. G.; Vaz, M.; DeJesus Damiao, D.; Oguri, V.; Santoro, A.; Sznajder, A.; DeMoraes Gregores, E.; Iope, R. L.; Novaes, S. F.; Tomei, T.; Anguelov, T.; Antchev, G.; Atanasov, I.; Damgov, J.; Darmenov, N.; Dimitrov, L.; Genchev, V.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Stoykova, S.; Sultanov, G.; Trayanov, R.; Vankov, I.; Cheshkov, C.; Dimitrov, A.; Dyulendarova, M.; Glushkov, I.; Kozhuharov, V.; Litov, L.; Makariev, M.; Marinova, E.; Markov, S.; Mateev, M.; Nasteva, I.; Pavlov, B.; Petev, P.; Petkov, P.; Spassov, V.; Toteva, Z.; Velev, V.; Verguilov, V.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Jiang, C. H.; Liu, B.; Shen, X. Y.; Sun, H. S.; Tao, J.; Wang, J.; Yang, M.; Zhang, Z.; Zhao, W. R.; Zhuang, H. L.; Ban, Y.; Cai, J.; Ge, Y. C.; Liu, S.; Liu, H. T.; Liu, L.; Qian, S. J.; Wang, Q.; Xue, Z. H.; Yang, Z. C.; Ye, Y. L.; Ying, J.; Li, P. J.; Liao, J.; Xue, Z. L.; Yan, D. S.; Yuan, H.; Carrillo Montoya, C. A.; Sanabria, J. C.; Godinovic, N.; Puljak, I.; Soric, I.; Antunovic, Z.; Dzelalija, M.; Marasovic, K.; Brigljevic, V.; Kadija, K.; Morovic, S.; Fereos, R.; Nicolaou, C.; Papadakis, A.; Ptochos, F.; Razis, P. A.; Tsiakkouri, D.; Zinonos, Z.; Hektor, A.; Kadastik, M.; Kannike, K.; Lippmaa, E.; Müntel, M.; Raidal, M.; Rebane, L.; Aarnio, P. A.; Anttila, E.; Banzuzi, K.; Bulteau, P.; Czellar, S.; Eiden, N.; Eklund, C.; Engstrom, P.; Heikkinen, A.; Honkanen, A.; Härkönen, J.; Karimäki, V.; Katajisto, H. M.; Kinnunen, R.; Klem, J.; Kortesmaa, J.; Kotamäki, M.; Kuronen, A.; Lampén, T.; Lassila-Perini, K.; Lefébure, V.; Lehti, S.; Lindén, T.; Luukka, P. R.; Michal, S.; Moura Brigido, F.; Mäenpää, T.; Nyman, T.; Nystén, J.; Pietarinen, E.; Skog, K.; Tammi, K.; Tuominen, E.; Tuominiemi, J.; Ungaro, D.; Vanhala, T. P.; Wendland, L.; Williams, C.; Iskanius, M.; Korpela, A.; Polese, G.; Tuuva, T.; Bassompierre, G.; Bazan, A.; David, P. Y.; Ditta, J.; Drobychev, G.; Fouque, N.; Guillaud, J. P.; Hermel, V.; Karneyeu, A.; LeFlour, T.; Lieunard, S.; Maire, M.; Mendiburu, P.; Nedelec, P.; Peigneux, J. P.; Schneegans, M.; Sillou, D.; Vialle, J. P.; Anfreville, M.; Bard, J. P.; Besson, P.; Bougamont, E.; Boyer, M.; Bredy, P.; Chipaux, R.; Dejardin, M.; Denegri, D.; Descamps, J.; Fabbro, B.; Faure, J. L.; Ganjour, S.; Gentit, F. X.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Jeanney, C.; Kircher, F.; Lemaire, M. C.; Lemoigne, Y.; Levesy, B.; Locci, E.; Lottin, J. P.; Mandjavidze, I.; Mur, M.; Pansart, J. P.; Payn, A.; Rander, J.; Reymond, J. M.; Rolquin, J.; Rondeaux, F.; Rosowsky, A.; Rousse, J. Y. A.; Sun, Z. H.; Tartas, J.; Van Lysebetten, A.; Venault, P.; Verrecchia, P.; Anduze, M.; Badier, J.; Baffioni, S.; Bercher, M.; Bernet, C.; Berthon, U.; Bourotte, J.; Busata, A.; Busson, P.; Cerutti, M.; Chamont, D.; Charlot, C.; Collard, C.; Debraine, A.; Decotigny, D.; Dobrzynski, L.; Ferreira, O.; Geerebaert, Y.; Gilly, J.; Gregory, C.; Guevara Riveros, L.; Haguenauer, M.; Karar, A.; Koblitz, B.; Lecouturier, D.; Mathieu, A.; Milleret, G.; Miné, P.; Paganini, P.; Poilleux, P.; Pukhaeva, N.; Regnault, N.; Romanteau, T.; Semeniouk, I.; Sirois, Y.; Thiebaux, C.; Vanel, J. C.; Zabi, A.; Agram, J. L.; Albert, A.; Anckenmann, L.; Andrea, J.; Anstotz, F.; Bergdolt, A. M.; Berst, J. D.; Blaes, R.; Bloch, D.; Brom, J. M.; Cailleret, J.; Charles, F.; Christophel, E.; Claus, G.; Coffin, J.; Colledani, C.; Croix, J.; Dangelser, E.; Dick, N.; Didierjean, F.; Drouhin, F.; Dulinski, W.; Ernenwein, J. P.; Fang, R.; Fontaine, J. C.; Gaudiot, G.; Geist, W.; Gelé, D.; Goeltzenlichter, T.; Goerlach, U.; Graehling, P.; Gross, L.; Hu, C. Guo; Helleboid, J. M.; Henkes, T.; Hoffer, M.; Hoffmann, C.; Hosselet, J.; Houchu, L.; Hu, Y.; Huss, D.; Illinger, C.; Jeanneau, F.; Juillot, P.; Kachelhoffer, T.; Kapp, M. R.; Kettunen, H.; Lakehal Ayat, L.; LeBihan, A. C.; Lounis, A.; Maazouzi, C.; Mack, V.; Majewski, P.; Mangeol, D.; Michel, J.; Moreau, S.; Olivetto, C.; Pallarès, A.; Patois, Y.; Pralavorio, P.; Racca, C.; Riahi, Y.; Ripp-Baudot, I.; Schmitt, P.; Schunck, J. P.; Schuster, G.; Schwaller, B.; Sigward, M. H.; Sohler, J. L.; Speck, J.; Strub, R.; Todorov, T.; Turchetta, R.; Van Hove, P.; Vintache, D.; Zghiche, A.; Ageron, M.; Augustin, J. E.; Baty, C.; Baulieu, G.; Bedjidian, M.; Blaha, J.; Bonnevaux, A.; Boudoul, G.; Brunet, P.; Chabanat, E.; Chabert, E. C.; Chierici, R.; Chorowicz, V.; Combaret, C.; Contardo, D.; Della Negra, R.; Depasse, P.; Drapier, O.; Dupanloup, M.; Dupasquier, T.; El Mamouni, H.; Estre, N.; Fay, J.; Gascon, S.; Giraud, N.; Girerd, C.; Guillot, G.; Haroutunian, R.; Ille, B.; Lethuillier, M.; Lumb, N.; Martin, C.; Mathez, H.; Maurelli, G.; Muanza, S.; Pangaud, P.; Perries, S.; Ravat, O.; Schibler, E.; Schirra, F.; Smadja, G.; Tissot, S.; Trocme, B.; Vanzetto, S.; Walder, J. P.; Bagaturia, Y.; Mjavia, D.; Mzhavia, A.; Tsamalaidze, Z.; Roinishvili, V.; Adolphi, R.; Anagnostou, G.; Brauer, R.; Braunschweig, W.; Esser, H.; Feld, L.; Karpinski, W.; Khomich, A.; Klein, K.; Kukulies, C.; Lübelsmeyer, K.; Olzem, J.; Ostaptchouk, A.; Pandoulas, D.; Pierschel, G.; Raupach, F.; Schael, S.; Schultz von Dratzig, A.; Schwering, G.; Siedling, R.; Thomas, M.; Weber, M.; Wittmer, B.; Wlochal, M.; Adamczyk, F.; Adolf, A.; Altenhöfer, G.; Bechstein, S.; Bethke, S.; Biallass, P.; Biebel, O.; Bontenackels, M.; Bosseler, K.; Böhm, A.; Erdmann, M.; Faissner, H.; Fehr, B.; Fesefeldt, H.; Fetchenhauer, G.; Frangenheim, J.; Frohn, J. H.; Grooten, J.; Hebbeker, T.; Hermann, S.; Hermens, E.; Hilgers, G.; Hoepfner, K.; Hof, C.; Jacobi, E.; Kappler, S.; Kirsch, M.; Kreuzer, P.; Kupper, R.; Lampe, H. R.; Lanske, D.; Mameghani, R.; Meyer, A.; Meyer, S.; Moers, T.; Müller, E.; Pahlke, R.; Philipps, B.; Rein, D.; Reithler, H.; Reuter, W.; Rütten, P.; Schulz, S.; Schwarthoff, H.; Sobek, W.; Sowa, M.; Stapelberg, T.; Szczesny, H.; Teykal, H.; Teyssier, D.; Tomme, H.; Tomme, W.; Tonutti, M.; Tsigenov, O.; Tutas, J.; Vandenhirtz, J.; Wagner, H.; Wegner, M.; Zeidler, C.; Beissel, F.; Davids, M.; Duda, M.; Flügge, G.; Giffels, M.; Hermanns, T.; Heydhausen, D.; Kalinin, S.; Kasselmann, S.; Kaussen, G.; Kress, T.; Linn, A.; Nowack, A.; Perchalla, L.; Poettgens, M.; Pooth, O.; Sauerland, P.; Stahl, A.; Tornier, D.; Zoeller, M. H.; Behrens, U.; Borras, K.; Flossdorf, A.; Hatton, D.; Hegner, B.; Kasemann, M.; Mankel, R.; Meyer, A.; Mnich, J.; Rosemann, C.; Youngman, C.; Zeuner, W. D.; Bechtel, F.; Buhmann, P.; Butz, E.; Flucke, G.; Hamdorf, R. H.; Holm, U.; Klanner, R.; Pein, U.; Schirm, N.; Schleper, P.; Steinbrück, G.; Van Staa, R.; Wolf, R.; Atz, B.; Barvich, T.; Blüm, P.; Boegelspacher, F.; Bol, H.; Chen, Z. Y.; Chowdhury, S.; DeBoer, W.; Dehm, P.; Dirkes, G.; Fahrer, M.; Felzmann, U.; Frey, M.; Furgeri, A.; Gregoriev, E.; Hartmann, F.; Hauler, F.; Heier, S.; Kärcher, K.; Ledermann, B.; Mueller, S.; Müller, Th; Neuberger, D.; Piasecki, C.; Quast, G.; Rabbertz, K.; Sabellek, A.; Scheurer, A.; Schilling, F. P.; Simonis, H. J.; Skiba, A.; Steck, P.; Theel, A.; Thümmel, W. H.; Trunov, A.; Vest, A.; Weiler, T.; Weiser, C.; Weseler, S.; Zhukov, V.; Barone, M.; Daskalakis, G.; Dimitriou, N.; Fanourakis, G.; Filippidis, C.; Geralis, T.; Kalfas, C.; Karafasoulis, K.; Koimas, A.; Kyriakis, A.; Kyriazopoulou, S.; Loukas, D.; Markou, A.; Markou, C.; Mastroyiannopoulos, N.; Mavrommatis, C.; Mousa, J.; Papadakis, I.; Petrakou, E.; Siotis, I.; Theofilatos, K.; Tzamarias, S.; Vayaki, A.; Vermisoglou, G.; Zachariadou, A.; Gouskos, L.; Karapostoli, G.; Katsas, P.; Panagiotou, A.; Papadimitropoulos, C.; Aslanoglou, X.; Evangelou, I.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Triantis, F. A.; Bencze, G.; Boldizsar, L.; Debreczeni, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Kovesarki, P.; Laszlo, A.; Odor, G.; Patay, G.; Sikler, F.; Veres, G.; Vesztergombi, G.; Zalan, P.; Fenyvesi, A.; Imrek, J.; Molnar, J.; Novak, D.; Palinkas, J.; Szekely, G.; Beni, N.; Kapusi, A.; Marian, G.; Radics, B.; Raics, P.; Szabo, Z.; Szillasi, Z.; Trocsanyi, Z. L.; Zilizi, G.; Bawa, H. S.; Beri, S. B.; Bhandari, V.; Bhatnagar, V.; Kaur, M.; Kohli, J. M.; Kumar, A.; Singh, B.; Singh, J. B.; Arora, S.; Bhattacharya, S.; Chatterji, S.; Chauhan, S.; Choudhary, B. C.; Gupta, P.; Jha, M.; Ranjan, K.; Shivpuri, R. K.; Srivastava, A. K.; Choudhury, R. K.; Dutta, D.; Ghodgaonkar, M.; Kailas, S.; Kataria, S. K.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, Sunanda; Bose, S.; Chendvankar, S.; Deshpande, P. V.; Guchait, M.; Gurtu, A.; Maity, M.; Majumder, G.; Mazumdar, K.; Nayak, A.; Patil, M. R.; Sharma, S.; Sudhakar, K.; Acharya, B. S.; Banerjee, Sudeshna; Bheesette, S.; Dugad, S.; Kalmani, S. D.; Lakkireddi, V. R.; Mondal, N. K.; Panyam, N.; Verma, P.; Arfaei, H.; Hashemi, M.; Najafabadi, M. Mohammadi; Moshaii, A.; Paktinat Mehdiabadi, S.; Felcini, M.; Grunewald, M.; Abadjiev, K.; Abbrescia, M.; Barbone, L.; Cariola, P.; Chiumarulo, F.; Clemente, A.; Colaleo, A.; Creanza, D.; DeFilippis, N.; DePalma, M.; DeRobertis, G.; Donvito, G.; Ferorelli, R.; Fiore, L.; Franco, M.; Giordano, D.; Guida, R.; Iaselli, G.; Lacalamita, N.; Loddo, F.; Maggi, G.; Maggi, M.; Manna, N.; Marangelli, B.; Mennea, M. S.; My, S.; Natali, S.; Nuzzo, S.; Papagni, G.; Pinto, C.; Pompili, A.; Pugliese, G.; Ranieri, A.; Romano, F.; Roselli, G.; Sala, G.; Selvaggi, G.; Silvestris, L.; Tempesta, P.; Trentadue, R.; Tupputi, S.; Zito, G.; Abbiendi, G.; Bacchi, W.; Battilana, C.; Benvenuti, A. C.; Boldini, M.; Bonacorsi, D.; Braibant-Giacomelli, S.; Cafaro, V. D.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Ciocca, C.; Codispoti, G.; Cuffiani, M.; D'Antone, I.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Finelli, S.; Giacomelli, P.; Giordano, V.; Giunta, M.; Grandi, C.; Guerzoni, M.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Odorici, F.; Paolucci, A.; Pellegrini, G.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Torromeo, G.; Travaglini, R.; Veronese, G. P.; Albergo, S.; Chiorboli, M.; Costa, S.; Galanti, M.; Gatto Rotondo, G.; Giudice, N.; Guardone, N.; Noto, F.; Potenza, R.; Saizu, M. A.; Salemi, G.; Sutera, C.; Tricomi, A.; Tuve, C.; Bellucci, L.; Brianzi, M.; Broccolo, G.; Catacchini, E.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Frosali, S.; Genta, C.; Landi, G.; Lenzi, P.; Macchiolo, A.; Maletta, F.; Manolescu, F.; Marchettini, C.; Masetti, L.; Mersi, S.; Meschini, M.; Minelli, C.; Paoletti, S.; Parrini, G.; Scarlini, E.; Sguazzoni, G.; Benussi, L.; Bertani, M.; Bianco, S.; Caponero, M.; Colonna, D.; Daniello, L.; Fabbri, F.; Felli, F.; Giardoni, M.; La Monaca, A.; Ortenzi, B.; Pallotta, M.; Paolozzi, A.; Paris, C.; Passamonti, L.; Pierluigi, D.; Ponzio, B.; Pucci, C.; Russo, A.; Saviano, G.; Fabbricatore, P.; Farinon, S.; Greco, M.; Musenich, R.; Badoer, S.; Berti, L.; Biasotto, M.; Fantinel, S.; Frizziero, E.; Gastaldi, U.; Gulmini, M.; Lelli, F.; Maron, G.; Squizzato, S.; Toniolo, N.; Traldi, S.; Banfi, S.; Bertoni, R.; Bonesini, M.; Carbone, L.; Cerati, G. B.; Chignoli, F.; D'Angelo, P.; DeMin, A.; Dini, P.; Farina, F. M.; Ferri, F.; Govoni, P.; Magni, S.; Malberti, M.; Malvezzi, S.; Mazza, R.; Menasce, D.; Miccio, V.; Moroni, L.; Negri, P.; Paganoni, M.; Pedrini, D.; Pullia, A.; Ragazzi, S.; Redaelli, N.; Rovere, M.; Sala, L.; Sala, S.; Salerno, R.; Tabarelli de Fatis, T.; Tancini, V.; Taroni, S.; Boiano, A.; Cassese, F.; Cassese, C.; Cimmino, A.; D'Aquino, B.; Lista, L.; Lomidze, D.; Noli, P.; Paolucci, P.; Passeggio, G.; Piccolo, D.; Roscilli, L.; Sciacca, C.; Vanzanella, A.; Azzi, P.; Bacchetta, N.; Barcellan, L.; Bellato, M.; Benettoni, M.; Bisello, D.; Borsato, E.; Candelori, A.; Carlin, R.; Castellani, L.; Checchia, P.; Ciano, L.; Colombo, A.; Conti, E.; Da Rold, M.; Dal Corso, F.; DeGiorgi, M.; DeMattia, M.; Dorigo, T.; Dosselli, U.; Fanin, C.; Galet, G.; Gasparini, F.; Gasparini, U.; Giraldo, A.; Giubilato, P.; Gonella, F.; Gresele, A.; Griggio, A.; Guaita, P.; Kaminskiy, A.; Karaevskii, S.; Khomenkov, V.; Kostylev, D.; Lacaprara, S.; Lazzizzera, I.; Lippi, I.; Loreti, M.; Margoni, M.; Martinelli, R.; Mattiazzo, S.; Mazzucato, M.; Meneguzzo, A. T.; Modenese, L.; Montecassiano, F.; Neviani, A.; Nigro, M.; Paccagnella, A.; Pantano, D.; Parenti, A.; Passaseo, M.; Pedrotta, R.; Pegoraro, M.; Rampazzo, G.; Reznikov, S.; Ronchese, P.; Sancho Daponte, A.; Sartori, P.; Stavitskiy, I.; Tessaro, M.; Torassa, E.; Triossi, A.; Vanini, S.; Ventura, S.; Ventura, L.; Verlato, M.; Zago, M.; Zatti, F.; Zotto, P.; Zumerle, G.; Baesso, P.; Belli, G.; Berzano, U.; Bricola, S.; Grelli, A.; Musitelli, G.; Nardò, R.; Necchi, M. M.; Pagano, D.; Ratti, S. P.; Riccardi, C.; Torre, P.; Vicini, A.; Vitulo, P.; Viviani, C.; Aisa, D.; Aisa, S.; Ambroglini, F.; Angarano, M. M.; Babucci, E.; Benedetti, D.; Biasini, M.; Bilei, G. M.; Bizzaglia, S.; Brunetti, M. T.; Caponeri, B.; Checcucci, B.; Covarelli, R.; Dinu, N.; Fanò, L.; Farnesini, L.; Giorgi, M.; Lariccia, P.; Mantovani, G.; Moscatelli, F.; Passeri, D.; Piluso, A.; Placidi, P.; Postolache, V.; Santinelli, R.; Santocchia, A.; Servoli, L.; Spiga, D.; Azzurri, P.; Bagliesi, G.; Balestri, G.; Basti, A.; Bellazzini, R.; Benucci, L.; Bernardini, J.; Berretta, L.; Bianucci, S.; Boccali, T.; Bocci, A.; Borrello, L.; Bosi, F.; Bracci, F.; Brez, A.; Calzolari, F.; Castaldi, R.; Cazzola, U.; Ceccanti, M.; Cecchi, R.; Cerri, C.; Cucoanes, A. S.; Dell'Orso, R.; Dobur, D.; Dutta, S.; Fiori, F.; Foà, L.; Gaggelli, A.; Gennai, S.; Giassi, A.; Giusti, S.; Kartashov, D.; Kraan, A.; Latronico, L.; Ligabue, F.; Linari, S.; Lomtadze, T.; Lungu, G. A.; Magazzu, G.; Mammini, P.; Mariani, F.; Martinelli, G.; Massa, M.; Messineo, A.; Moggi, A.; Palla, F.; Palmonari, F.; Petragnani, G.; Petrucciani, G.; Profeti, A.; Raffaelli, F.; Rizzi, D.; Sanguinetti, G.; Sarkar, S.; Segneri, G.; Sentenac, D.; Serban, A. T.; Slav, A.; Spagnolo, P.; Spandre, G.; Tenchini, R.; Tolaini, S.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Vos, M.; Zaccarelli, L.; Baccaro, S.; Barone, L.; Bartoloni, A.; Borgia, B.; Capradossi, G.; Cavallari, F.; Cecilia, A.; D'Angelo, D.; Dafinei, I.; DelRe, D.; Di Marco, E.; Diemoz, M.; Ferrara, G.; Gargiulo, C.; Guerra, S.; Iannone, M.; Longo, E.; Montecchi, M.; Nuccetelli, M.; Organtini, G.; Palma, A.; Paramatti, R.; Pellegrino, F.; Rahatlou, S.; Rovelli, C.; Safai Tehrani, F.; Zullo, A.; Alampi, G.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bellan, R.; Benotto, F.; Biino, C.; Bolognesi, S.; Borgia, M. A.; Botta, C.; Brasolin, A.; Cartiglia, N.; Castello, R.; Cerminara, G.; Cirio, R.; Cordero, M.; Costa, M.; Dattola, D.; Daudo, F.; Dellacasa, G.; Demaria, N.; Dughera, G.; Dumitrache, F.; Farano, R.; Ferrero, G.; Filoni, E.; Kostyleva, G.; Larsen, H. E.; Mariotti, C.; Marone, M.; Maselli, S.; Menichetti, E.; Mereu, P.; Migliore, E.; Mila, G.; Monaco, V.; Musich, M.; Nervo, M.; Obertino, M. M.; Panero, R.; Parussa, A.; Pastrone, N.; Peroni, C.; Petrillo, G.; Romero, A.; Ruspa, M.; Sacchi, R.; Scalise, M.; Solano, A.; Staiano, A.; Trapani, P. P.; Trocino, D.; Vaniev, V.; Vilela Pereira, A.; Zampieri, A.; Belforte, S.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; Kavka, C.; Penzo, A.; Kim, Y. E.; Nam, S. K.; Kim, D. H.; Kim, G. N.; Kim, J. C.; Kong, D. J.; Ro, S. R.; Son, D. C.; Park, S. Y.; Kim, Y. J.; Kim, J. Y.; Lim, I. T.; Pac, M. Y.; Lee, S. J.; Jung, S. Y.; Rhee, J. T.; Ahn, S. H.; Hong, B. S.; Jeng, Y. K.; Kang, M. H.; Kim, H. C.; Kim, J. H.; Kim, T. J.; Lee, K. S.; Lim, J. K.; Moon, D. H.; Park, I. C.; Park, S. K.; Ryu, M. S.; Sim, K.-S.; Son, K. J.; Hong, S. J.; Choi, Y. I.; Castilla Valdez, H.; Sanchez Hernandez, A.; Carrillo Moreno, S.; Morelos Pineda, A.; Aerts, A.; Van der Stok, P.; Weffers, H.; Allfrey, P.; Gray, R. N. C.; Hashimoto, M.; Krofcheck, D.; Bell, A. J.; Bernardino Rodrigues, N.; Butler, P. H.; Churchwell, S.; Knegjens, R.; Whitehead, S.; Williams, J. C.; Aftab, Z.; Ahmad, U.; Ahmed, I.; Ahmed, W.; Asghar, M. I.; Asghar, S.; Dad, G.; Hafeez, M.; Hoorani, H. R.; Hussain, I.; Hussain, N.; Iftikhar, M.; Khan, M. S.; Mehmood, K.; Osman, A.; Shahzad, H.; Zafar, A. R.; Ali, A.; Bashir, A.; Jan, A. M.; Kamal, A.; Khan, F.; Saeed, M.; Tanwir, S.; Zafar, M. A.; Blocki, J.; Cyz, A.; Gladysz-Dziadus, E.; Mikocki, S.; Rybczynski, M.; Turnau, J.; Wlodarczyk, Z.; Zychowski, P.; Bunkowski, K.; Cwiok, M.; Czyrkowski, H.; Dabrowski, R.; Dominik, W.; Doroba, K.; Kalinowski, A.; Kierzkowski, K.; Konecki, M.; Krolikowski, J.; Kudla, I. M.; Pietrusinski, M.; Pozniak, K.; Zabolotny, W.; Zych, P.; Gokieli, R.; Goscilo, L.; Górski, M.; Nawrocki, K.; Traczyk, P.; Wrochna, G.; Zalewski, P.; Pozniak, K. T.; Romaniuk, R.; Zabolotny, W. M.; Alemany-Fernandez, R.; Almeida, C.; Almeida, N.; Araujo Vila Verde, A. S.; Barata Monteiro, T.; Bluj, M.; Da Mota Silva, S.; Tinoco Mendes, A. David; Freitas Ferreira, M.; Gallinaro, M.; Husejko, M.; Jain, A.; Kazana, M.; Musella, P.; Nobrega, R.; Rasteiro Da Silva, J.; Ribeiro, P. Q.; Santos, M.; Silva, P.; Silva, S.; Teixeira, I.; Teixeira, J. P.; Varela, J.; Varner, G.; Vaz Cardoso, N.; Altsybeev, I.; Babich, K.; Belkov, A.; Belotelov, I.; Bunin, P.; Chesnevskaya, S.; Elsha, V.; Ershov, Y.; Filozova, I.; Finger, M.; Finger, M., Jr.; Golunov, A.; Golutvin, I.; Gorbounov, N.; Gramenitski, I.; Kalagin, V.; Kamenev, A.; Karjavin, V.; Khabarov, S.; Khabarov, V.; Kiryushin, Y.; Konoplyanikov, V.; Korenkov, V.; Kozlov, G.; Kurenkov, A.; Lanev, A.; Lysiakov, V.; Malakhov, A.; Melnitchenko, I.; Mitsyn, V. V.; Moisenz, K.; Moisenz, P.; Movchan, S.; Nikonov, E.; Oleynik, D.; Palichik, V.; Perelygin, V.; Petrosyan, A.; Rogalev, E.; Samsonov, V.; Savina, M.; Semenov, R.; Sergeev, S.; Shmatov, S.; Shulha, S.; Smirnov, V.; Smolin, D.; Tcheremoukhine, A.; Teryaev, O.; Tikhonenko, E.; Urkinbaev, A.; Vasil'ev, S.; Vishnevskiy, A.; Volodko, A.; Zamiatin, N.; Zarubin, A.; Zarubin, P.; Zubarev, E.; Bondar, N.; Gavrikov, Y.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Kozlov, V.; Lebedev, V.; Makarenkov, G.; Moroz, F.; Neustroev, P.; Obrant, G.; Orishchin, E.; Petrunin, A.; Shcheglov, Y.; Shchetkovskiy, A.; Sknar, V.; Skorobogatov, V.; Smirnov, I.; Sulimov, V.; Tarakanov, V.; Uvarov, L.; Vavilov, S.; Velichko, G.; Volkov, S.; Vorobyev, A.; Chmelev, D.; Druzhkin, D.; Ivanov, A.; Kudinov, V.; Logatchev, O.; Onishchenko, S.; Orlov, A.; Sakharov, V.; Smetannikov, V.; Tikhomirov, A.; Zavodthikov, S.; Andreev, Yu; Anisimov, A.; Duk, V.; Gninenko, S.; Golubev, N.; Gorbunov, D.; Kirsanov, M.; Krasnikov, N.; Matveev, V.; Pashenkov, A.; Pastsyak, A.; Postoev, V. E.; Sadovski, A.; Skassyrskaia, A.; Solovey, Alexander; Solovey, Anatoly; Soloviev, D.; Toropin, A.; Troitsky, S.; Alekhin, A.; Baldov, A.; Epshteyn, V.; Gavrilov, V.; Ilina, N.; Kaftanov, V.; Karpishin, V.; Kiselevich, I.; Kolosov, V.; Kossov, M.; Krokhotin, A.; Kuleshov, S.; Oulianov, A.; Pozdnyakov, A.; Safronov, G.; Semenov, S.; Stepanov, N.; Stolin, V.; Vlasov, E.; Zaytsev, V.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Eyyubova, G.; Gribushin, A.; Ilyin, V.; Klyukhin, V.; Kodolova, O.; Kruglov, N. A.; Kryukov, A.; Lokhtin, I.; Malinina, L.; Mikhaylin, V.; Petrushanko, S.; Sarycheva, L.; Savrin, V.; Shamardin, L.; Sherstnev, A.; Snigirev, A.; Teplov, K.; Vardanyan, I.; Fomenko, A. M.; Konovalova, N.; Kozlov, V.; Lebedev, A. I.; Lvova, N.; Rusakov, S. V.; Terkulov, A.; Abramov, V.; Akimenko, S.; Artamonov, A.; Ashimova, A.; Azhgirey, I.; Bitioukov, S.; Chikilev, O.; Datsko, K.; Filine, A.; Godizov, A.; Goncharov, P.; Grishin, V.; Inyakin, A.; Kachanov, V.; Kalinin, A.; Khmelnikov, A.; Konstantinov, D.; Korablev, A.; Krychkine, V.; Krinitsyn, A.; Levine, A.; Lobov, I.; Lukanin, V.; Mel'nik, Y.; Molchanov, V.; Petrov, V.; Petukhov, V.; Pikalov, V.; Ryazanov, A.; Ryutin, R.; Shelikhov, V.; Skvortsov, V.; Slabospitsky, S.; Sobol, A.; Sytine, A.; Talov, V.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Zelepoukine, S.; Lukyanov, V.; Mamaeva, G.; Prilutskaya, Z.; Rumyantsev, I.; Sokha, S.; Tataurschikov, S.; Vasilyev, I.; Adzic, P.; Anicin, I.; Djordjevic, M.; Jovanovic, D.; Maletic, D.; Puzovic, J.; Smiljkovic, N.; Aguayo Navarrete, E.; Aguilar-Benitez, M.; Ahijado Munoz, J.; Alarcon Vega, J. M.; Alberdi, J.; Alcaraz Maestre, J.; Aldaya Martin, M.; Arce, P.; Barcala, J. M.; Berdugo, J.; Blanco Ramos, C. L.; Burgos Lazaro, C.; Caballero Bejar, J.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Chercoles Catalán, J. J.; Colino, N.; Daniel, M.; DeLa Cruz, B.; Delgado Peris, A.; Fernandez Bedoya, C.; Ferrando, A.; Fouz, M. C.; Francia Ferrero, D.; Garcia Romero, J.; Garcia-Abia, P.; Gonzalez Lopez, O.; Hernandez, J. M.; Josa, M. I.; Marin, J.; Merino, G.; Molinero, A.; Navarrete, J. J.; Oller, J. C.; Puerta Pelayo, J.; Puras Sanchez, J. C.; Ramirez, J.; Romero, L.; Villanueva Munoz, C.; Willmott, C.; Yuste, C.; Albajar, C.; de Trocóniz, J. F.; Jimenez, I.; Macias, R.; Teixeira, R. F.; Cuevas, J.; Fernández Menéndez, J.; Gonzalez Caballero, I.; Lopez-Garcia, J.; Naves Sordo, H.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Cano Fernandez, D.; Diaz Merino, I.; Duarte Campderros, J.; Fernandez, M.; Fernandez Menendez, J.; Figueroa, C.; Garcia Moral, L. A.; Gomez, G.; Gomez Casademunt, F.; Gonzalez Sanchez, J.; Gonzalez Suarez, R.; Jorda, C.; Lobelle Pardo, P.; Lopez Garcia, A.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Martinez Ruiz del Arbol, P.; Matorras, F.; Orviz Fernandez, P.; Patino Revuelta, A.; Rodrigo, T.; Rodriguez Gonzalez, D.; Ruiz Jimeno, A.; Scodellaro, L.; Sobron Sanudo, M.; Vila, I.; Vilar Cortabitarte, R.; Barbero, M.; Goldin, D.; Henrich, B.; Tauscher, L.; Vlachos, S.; Wadhwa, M.; Abbaneo, D.; Abbas, S. M.; Ahmed, I.; Akhtar, S.; Akhtar, M. I.; Albert, E.; Alidra, M.; Ashby, S.; Aspell, P.; Auffray, E.; Baillon, P.; Ball, A.; Bally, S. L.; Bangert, N.; Barillère, R.; Barney, D.; Beauceron, S.; Beaudette, F.; Benelli, G.; Benetta, R.; Benichou, J. L.; Bialas, W.; Bjorkebo, A.; Blechschmidt, D.; Bloch, C.; Bloch, P.; Bonacini, S.; Bos, J.; Bosteels, M.; Boyer, V.; Branson, A.; Breuker, H.; Bruneliere, R.; Buchmuller, O.; Campi, D.; Camporesi, T.; Caner, A.; Cano, E.; Carrone, E.; Cattai, A.; Chatelain, J. P.; Chauvey, M.; Christiansen, T.; Ciganek, M.; Cittolin, S.; Cogan, J.; Conde Garcia, A.; Cornet, H.; Corrin, E.; Corvo, M.; Cucciarelli, S.; Curé, B.; D'Enterria, D.; DeRoeck, A.; de Visser, T.; Delaere, C.; Delattre, M.; Deldicque, C.; Delikaris, D.; Deyrail, D.; Di Vincenzo, S.; Domeniconi, A.; Dos Santos, S.; Duthion, G.; Edera, L. M.; Elliott-Peisert, A.; Eppard, M.; Fanzago, F.; Favre, M.; Foeth, H.; Folch, R.; Frank, N.; Fratianni, S.; Freire, M. A.; Frey, A.; Fucci, A.; Funk, W.; Gaddi, A.; Gagliardi, F.; Gastal, M.; Gateau, M.; Gayde, J. C.; Gerwig, H.; Ghezzi, A.; Gigi, D.; Gill, K.; Giolo-Nicollerat, A. S.; Girod, J. P.; Glege, F.; Glessing, W.; Gomez-Reino Garrido, R.; Goudard, R.; Grabit, R.; Grillet, J. P.; Gutierrez Llamas, P.; Gutierrez Mlot, E.; Gutleber, J.; Hall-wilton, R.; Hammarstrom, R.; Hansen, M.; Harvey, J.; Hervé, A.; Hill, J.; Hoffmann, H. F.; Holzner, A.; Honma, A.; Hufnagel, D.; Huhtinen, M.; Ilie, S. D.; Innocente, V.; Jank, W.; Janot, P.; Jarron, P.; Jeanrenaud, M.; Jouvel, P.; Kerkach, R.; Kloukinas, K.; Kottelat, L. J.; Labbé, J. C.; Lacroix, D.; Lagrue, X.; Lasseur, C.; Laure, E.; Laurens, J. F.; Lazeyras, P.; LeGoff, J. M.; Lebeau, M.; Lecoq, P.; Lemeilleur, F.; Lenzi, M.; Leonardo, N.; Leonidopoulos, C.; Letheren, M.; Liendl, M.; Limia-Conde, F.; Linssen, L.; Ljuslin, C.; Lofstedt, B.; Loos, R.; Lopez Perez, J. A.; Lourenco, C.; Lyonnet, A.; Machard, A.; Mackenzie, R.; Magini, N.; Maire, G.; Malgeri, L.; Malina, R.; Mannelli, M.; Marchioro, A.; Martin, J.; Meijers, F.; Meridiani, P.; Meschi, E.; Meyer, T.; Meynet Cordonnier, A.; Michaud, J. F.; Mirabito, L.; Moser, R.; Mossiere, F.; Muffat-Joly, J.; Mulders, M.; Mulon, J.; Murer, E.; Mättig, P.; Oh, A.; Onnela, A.; Oriunno, M.; Orsini, L.; Osborne, J. A.; Paillard, C.; Pal, I.; Papotti, G.; Passardi, G.; Patino-Revuelta, A.; Patras, V.; Perea Solano, B.; Perez, E.; Perinic, G.; Pernot, J. F.; Petagna, P.; Petiot, P.; Petit, P.; Petrilli, A.; Pfeiffer, A.; Piccut, C.; Pimiä, M.; Pintus, R.; Pioppi, M.; Placci, A.; Pollet, L.; Postema, H.; Price, M. J.; Principe, R.; Racz, A.; Radermacher, E.; Ranieri, R.; Raymond, G.; Rebecchi, P.; Rehn, J.; Reynaud, S.; Rezvani Naraghi, H.; Ricci, D.; Ridel, M.; Risoldi, M.; Rodrigues Simoes Moreira, P.; Rohlev, A.; Roiron, G.; Rolandi, G.; Rumerio, P.; Runolfsson, O.; Ryjov, V.; Sakulin, H.; Samyn, D.; Santos Amaral, L. C.; Sauce, H.; Sbrissa, E.; Scharff-Hansen, P.; Schieferdecker, P.; Schlatter, W. D.; Schmitt, B.; Schmuecker, H. G.; Schröder, M.; Schwick, C.; Schäfer, C.; Segoni, I.; Sempere Roldán, P.; Sgobba, S.; Sharma, A.; Siegrist, P.; Sigaud, C.; Sinanis, N.; Sobrier, T.; Sphicas, P.; Spiropulu, M.; Stefanini, G.; Strandlie, A.; Szoncsó, F.; Taylor, B. G.; Teller, O.; Thea, A.; Tournefier, E.; Treille, D.; Tropea, P.; Troska, J.; Tsesmelis, E.; Tsirou, A.; Valls, J.; Van Vulpen, I.; Vander Donckt, M.; Vasey, F.; Vazquez Acosta, M.; Veillet, L.; Vichoudis, P.; Waurick, G.; Wellisch, J. P.; Wertelaers, P.; Wilhelmsson, M.; Willers, I. M.; Winkler, M.; Zanetti, M.; Bertl, W.; Deiters, K.; Dick, P.; Erdmann, W.; Feichtinger, D.; Gabathuler, K.; Hochman, Z.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; König, S.; Poerschke, P.; Renker, D.; Rohe, T.; Sakhelashvili, T.; Starodumov, A.; Aleksandrov, V.; Behner, F.; Beniozef, I.; Betev, B.; Blau, B.; Brett, A. M.; Caminada, L.; Chen, Z.; Chivarov, N.; Da Silva Di Calafiori, D.; Dambach, S.; Davatz, G.; Delachenal, V.; Della Marina, R.; Dimov, H.; Dissertori, G.; Dittmar, M.; Djambazov, L.; Dröge, M.; Eggel, C.; Ehlers, J.; Eichler, R.; Elmiger, M.; Faber, G.; Freudenreich, K.; Fuchs, J. F.; Georgiev, G. M.; Grab, C.; Haller, C.; Herrmann, J.; Hilgers, M.; Hintz, W.; Hofer, Hans; Hofer, Heinz; Horisberger, U.; Horvath, I.; Hristov, A.; Humbertclaude, C.; Iliev, B.; Kastli, W.; Kruse, A.; Kuipers, J.; Langenegger, U.; Lecomte, P.; Lejeune, E.; Leshev, G.; Lesmond, C.; List, B.; Luckey, P. D.; Lustermann, W.; Maillefaud, J. D.; Marchica, C.; Maurisset, A.; Meier, B.; Milenovic, P.; Milesi, M.; Moortgat, F.; Nanov, I.; Nardulli, A.; Nessi-Tedaldi, F.; Panev, B.; Pape, L.; Pauss, F.; Petrov, E.; Petrov, G.; Peynekov, M. M.; Pitzl, D.; Punz, T.; Riboni, P.; Riedlberger, J.; Rizzi, A.; Ronga, F. J.; Roykov, P. A.; Röser, U.; Schinzel, D.; Schöning, A.; Sourkov, A.; Stanishev, K.; Stoenchev, S.; Stöckli, F.; Suter, H.; Trüb, P.; Udriot, S.; Uzunova, D. G.; Veltchev, I.; Viertel, G.; von Gunten, H. P.; Waldmeier-Wicki, S.; Weber, R.; Weber, M.; Weng, J.; Wensveen, M.; Wittgenstein, F.; Zagoursky, K.; Alagoz, E.; Amsler, C.; Chiochia, V.; Hoermann, C.; Regenfus, C.; Robmann, P.; Rommerskirchen, T.; Schmidt, A.; Steiner, S.; Tsirigkas, D.; Wilke, L.; Blyth, S.; Chang, Y. H.; Chen, E. A.; Go, A.; Hung, C. C.; Kuo, C. M.; Li, S. W.; Lin, W.; Chang, P.; Chao, Y.; Chen, K. F.; Gao, Z.; Hou, G. W. S.; Hsiung, Y. B.; Lei, Y. J.; Lin, S. W.; Lu, R. S.; Shiu, J. G.; Tzeng, Y. M.; Ueno, K.; Velikzhanin, Y.; Wang, C. C.; Wang, M.-Z.; Aydin, S.; Azman, A.; Bakirci, M. N.; Basegmez, S.; Cerci, S.; Dumanoglu, I.; Erturk, S.; Eskut, E.; Kayis Topaksu, A.; Kisoglu, H.; Kurt, P.; Ozdemir, K.; Ozdes Koca, N.; Ozkurt, H.; Ozturk, S.; Polatöz, A.; Sogut, K.; Topakli, H.; Vergili, M.; Önengüt, G.; Gamsizkan, H.; Sekmen, S.; Serin-Zeyrek, M.; Sever, R.; Zeyrek, M.; Deliomeroglu, M.; Gülmez, E.; Isiksal, E.; Kaya, M.; Kaya, O.; Ozkorucuklu, S.; Sonmez, N.; Grinev, B.; Lyubynskiy, V.; Senchyshyn, V.; Levchuk, L.; Lukyanenko, S.; Soroka, D.; Sorokin, P.; Zub, S.; Anjum, A.; Baker, N.; Hauer, T.; McClatchey, R.; Odeh, M.; Rogulin, D.; Solomonides, A.; Brooke, J. J.; Croft, R.; Cussans, D.; Evans, D.; Frazier, R.; Grant, N.; Hansen, M.; Head, R. D.; Heath, G. P.; Heath, H. F.; Hill, C.; Huckvale, B.; Jackson, J.; Lynch, C.; Mackay, C. K.; Metson, S.; Nash, S. J.; Newbold, D. M.; Presland, A. D.; Probert, M. G.; Reid, E. C.; Smith, V. J.; Tapper, R. J.; Walton, R.; Bateman, E.; Bell, K. W.; Brown, R. M.; Camanzi, B.; Church, I. T.; Cockerill, D. J. A.; Cole, J. E.; Connolly, J. F.; Coughlan, J. A.; Flower, P. S.; Ford, P.; Francis, V. B.; French, M. J.; Galagedera, S. B.; Gannon, W.; Gay, A. P. R.; Geddes, N. I.; Greenhalgh, R. J. S.; Halsall, R. N. J.; Haynes, W. J.; Hill, J. A.; Jacob, F. R.; Jeffreys, P. W.; Jones, L. L.; Kennedy, B. W.; Lintern, A. L.; Lodge, A. B.; Maddox, A. J.; Morrissey, Q. R.; Murray, P.; Patrick, G. N.; Pattison, C. A. X.; Pearson, M. R.; Quinton, S. P. H.; Rogers, G. J.; Salisbury, J. G.; Shah, A. A.; Shepherd-Themistocleous, C. H.; Smith, B. J.; Sproston, M.; Stephenson, R.; Taghavi, S.; Tomalin, I. R.; Torbet, M. J.; Williams, J. H.; Womersley, W. J.; Worm, S. D.; Xing, F.; Apollonio, M.; Arteche, F.; Bainbridge, R.; Barber, G.; Barrillon, P.; Batten, J.; Beuselinck, R.; Brambilla Hall, P. M.; Britton, D.; Cameron, W.; Clark, D. E.; Clark, I. W.; Colling, D.; Cripps, N.; Davies, G.; Della Negra, M.; Dewhirst, G.; Dris, S.; Foudas, C.; Fulcher, J.; Futyan, D.; Graham, D. J.; Greder, S.; Greenwood, S.; Hall, G.; Hassard, J. F.; Hays, J.; Iles, G.; Kasey, V.; Khaleeq, M.; Leaver, J.; Lewis, P.; MacEvoy, B. C.; Maroney, O.; McLeod, E. M.; Miller, D. G.; Nash, J.; Nikitenko, A.; Noah Messomo, E.; Noy, M.; Papageorgiou, A.; Pesaresi, M.; Petridis, K.; Price, D. R.; Qu, X.; Raymond, D. M.; Rose, A.; Rutherford, S.; Ryan, M. J.; Sciacca, F.; Seez, C.; Sharp, P.; Sidiropoulos, G.; Stettler, M.; Stoye, M.; Striebig, J.; Takahashi, M.; Tallini, H.; Tapper, A.; Timlin, C.; Toudup, L.; Virdee, T.; Wakefield, S.; Walsham, P.; Wardrope, D.; Wingham, M.; Zhang, Y.; Zorba, O.; Da Via, C.; Goitom, I.; Hobson, P. R.; Imrie, D. C.; Reid, I.; Selby, C.; Sharif, O.; Teodorescu, L.; Watts, S. J.; Yaselli, I.; Hazen, E.; Heering, A.; Heister, A.; Lawlor, C.; Lazic, D.; Machado, E.; Rohlf, J.; Sulak, L.; Varela Rodriguez, F.; Wu, S. X.; Avetisyan, A.; Bose, T.; Christofek, L.; Cutts, D.; Esen, S.; Hooper, R.; Landsberg, G.; Narain, M.; Nguyen, D.; Speer, T.; Tsang, K. V.; Breedon, R.; Case, M.; Chertok, M.; Conway, J.; Cox, P. T.; Dolen, J.; Erbacher, R.; Fisyak, Y.; Friis, E.; Grim, G.; Holbrook, B.; Ko, W.; Kopecky, A.; Lander, R.; Lin, F. C.; Lister, A.; Maruyama, S.; Pellett, D.; Rowe, J.; Searle, M.; Smith, J.; Soha, A.; Squires, M.; Tripathi, M.; Vasquez Sierra, R.; Veelken, C.; Andreev, V.; Arisaka, K.; Bonushkin, Y.; Chandramouly, S.; Cline, D.; Cousins, R.; Erhan, S.; Hauser, J.; Ignatenko, M.; Jarvis, C.; Lisowski, B.; Matthey, C.; Mohr, B.; Mumford, J.; Otwinowski, S.; Pischalnikov, Y.; Rakness, G.; Schlein, P.; Shi, Y.; Tannenbaum, B.; Tucker, J.; Valuev, V.; Wallny, R.; Wang, H. G.; Yang, X.; Zheng, Y.; Andreeva, J.; Babb, J.; Campana, S.; Chrisman, D.; Clare, R.; Ellison, J.; Fortin, D.; Gary, J. W.; Gorn, W.; Hanson, G.; Jeng, G. Y.; Kao, S. C.; Layter, J. G.; Liu, F.; Liu, H.; Luthra, A.; Pasztor, G.; Rick, H.; Satpathy, A.; Shen, B. C.; Stringer, R.; Sytnik, V.; Tran, P.; Villa, S.; Wilken, R.; Wimpenny, S.; Zer-Zion, D.; Branson, J. G.; Coarasa Perez, J. A.; Dusinberre, E.; Kelley, R.; Lebourgeois, M.; Letts, J.; Lipeles, E.; Mangano, B.; Martin, T.; Mojaver, M.; Muelmenstaedt, J.; Norman, M.; Paar, H. P.; Petrucci, A.; Pi, H.; Pieri, M.; Rana, A.; Sani, M.; Sharma, V.; Simon, S.; White, A.; Würthwein, F.; Yagil, A.; Affolder, A.; Allen, A.; Campagnari, C.; D'Alfonso, M.; Dierlamm, A.; Garberson, J.; Hale, D.; Incandela, J.; Kalavase, P.; Koay, S. A.; Kovalskyi, D.; Krutelyov, V.; Kyre, S.; Lamb, J.; Lowette, S.; Nikolic, M.; Pavlunin, V.; Rebassoo, F.; Ribnik, J.; Richman, J.; Rossin, R.; Shah, Y. S.; Stuart, D.; Swain, S.; Vlimant, J. R.; White, D.; Witherell, M.; Bornheim, A.; Bunn, J.; Chen, J.; Denis, G.; Galvez, P.; Gataullin, M.; Legrand, I.; Litvine, V.; Ma, Y.; Mao, R.; Nae, D.; Narsky, I.; Newman, H. B.; Orimoto, T.; Rogan, C.; Shevchenko, S.; Steenberg, C.; Su, X.; Thomas, M.; Timciuc, V.; van Lingen, F.; Veverka, J.; Voicu, B. R.; Weinstein, A.; Wilkinson, R.; Xia, Y.; Yang, Y.; Zhang, L. Y.; Zhu, K.; Zhu, R. Y.; Ferguson, T.; Jang, D. W.; Jun, S. Y.; Paulini, M.; Russ, J.; Terentyev, N.; Vogel, H.; Vorobiev, I.; Bunce, M.; Cumalat, J. P.; Dinardo, M. E.; Drell, B. R.; Ford, W. T.; Givens, K.; Heyburn, B.; Johnson, D.; Nauenberg, U.; Stenson, K.; Wagner, S. R.; Agostino, L.; Alexander, J.; Blekman, F.; Cassel, D.; Das, S.; Duboscq, J. E.; Gibbons, L. K.; Heltsley, B.; Jones, C. D.; Kuznetsov, V.; Patterson, J. R.; Riley, D.; Ryd, A.; Stroiney, S.; Sun, W.; Thom, J.; Vaughan, J.; Wittich, P.; Beetz, C. P.; Cirino, G.; Podrasky, V.; Sanzeni, C.; Winn, D.; Abdullin, S.; Afaq, M. A.; Albrow, M.; Amundson, J.; Apollinari, G.; Atac, M.; Badgett, W.; Bakken, J. A.; Baldin, B.; Banicz, K.; Bauerdick, L. A. T.; Baumbaugh, A.; Berryhill, J.; Bhat, P. C.; Binkley, M.; Bloch, I.; Borcherding, F.; Boubekeur, A.; Bowden, M.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chevenier, G.; Chlebana, F.; Churin, I.; Cihangir, S.; Dagenhart, W.; Demarteau, M.; Dykstra, D.; Eartly, D. P.; Elias, J. E.; Elvira, V. D.; Evans, D.; Fisk, I.; Freeman, J.; Gaines, I.; Gartung, P.; Geurts, F. J. M.; Giacchetti, L.; Glenzinski, D. A.; Gottschalk, E.; Grassi, T.; Green, D.; Grimm, C.; Guo, Y.; Gutsche, O.; Hahn, A.; Hanlon, J.; Harris, R. M.; Hesselroth, T.; Holm, S.; Holzman, B.; James, E.; Jensen, H.; Johnson, M.; Joshi, U.; Klima, B.; Kossiakov, S.; Kousouris, K.; Kowalkowski, J.; Kramer, T.; Kwan, S.; Lei, C. M.; Leininger, M.; Los, S.; Lueking, L.; Lukhanin, G.; Lusin, S.; Maeshima, K.; Marraffino, J. M.; Mason, D.; McBride, P.; Miao, T.; Moccia, S.; Mokhov, N.; Mrenna, S.; Murray, S. J.; Newman-Holmes, C.; Noeding, C.; O'Dell, V.; Paterno, M.; Petravick, D.; Pordes, R.; Prokofyev, O.; Ratnikova, N.; Ronzhin, A.; Sekhri, V.; Sexton-Kennedy, E.; Sfiligoi, I.; Shaw, T. M.; Skup, E.; Smith, R. P.; Spalding, W. J.; Spiegel, L.; Stavrianakou, M.; Stiehr, G.; Stone, A. L.; Suzuki, I.; Tan, P.; Tanenbaum, W.; Temple, L. E.; Tkaczyk, S.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Wands, R.; Wenzel, H.; Whitmore, J.; Wicklund, E.; Wu, W. M.; Wu, Y.; Yarba, J.; Yarba, V.; Yumiceva, F.; Yun, J. C.; Zimmerman, T.; Acosta, D.; Avery, P.; Barashko, V.; Bartalini, P.; Bourilkov, D.; Cavanaugh, R.; Dolinsky, S.; Drozdetskiy, A.; Field, R. D.; Fu, Y.; Furic, I. K.; Gorn, L.; Holmes, D.; Kim, B. J.; Klimenko, S.; Konigsberg, J.; Korytov, A.; Kotov, K.; Levchenko, P.; Madorsky, A.; Matchev, K.; Mitselmakher, G.; Pakhotin, Y.; Prescott, C.; Ramond, L.; Ramond, P.; Schmitt, M.; Scurlock, B.; Stasko, J.; Stoeck, H.; Wang, D.; Yelton, J.; Gaultney, V.; Kramer, L.; Lebolo, L. M.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Atramentov, O.; Bertoldi, M.; Dharmaratna, W. G. D.; Gershtein, Y.; Gleyzer, S. V.; Hagopian, S.; Hagopian, V.; Jenkins, C. J.; Johnson, K. F.; Prosper, H.; Simek, D.; Thomaston, J.; Baarmand, M.; Baksay, L.; Guragain, S.; Hohlmann, M.; Mermerkaya, H.; Ralich, R.; Vodopiyanov, I.; Adams, M. R.; Anghel, I. M.; Apanasevich, L.; Barannikova, O.; Bazterra, V. E.; Betts, R. R.; Dragoiu, C.; Garcia-Solis, E. J.; Gerber, C. E.; Hofman, D. J.; Hollis, R.; Iordanova, A.; Khalatian, S.; Mironov, C.; Shabalina, E.; Smoron, A.; Varelas, N.; Akgun, U.; Albayrak, E. A.; Ayan, A. S.; Briggs, R.; Cankocak, K.; Clarida, W.; Cooper, A.; Debbins, P.; Duru, F.; Fountain, M.; McCliment, E.; Merlo, J. P.; Mestvirishvili, A.; Miller, M. J.; Moeller, A.; Newsom, C. R.; Norbeck, E.; Olson, J.; Onel, Y.; Perera, L.; Schmidt, I.; Wang, S.; Yetkin, T.; Anderson, E. W.; Chakir, H.; Hauptman, J. M.; Lamsa, J.; Barnett, B. A.; Blumenfeld, B.; Chien, C. Y.; Giurgiu, G.; Gritsan, A.; Kim, D. W.; Lae, C. K.; Maksimovic, P.; Swartz, M.; Tran, N.; Baringer, P.; Bean, A.; Chen, J.; Coppage, D.; Grachov, O.; Murray, M.; Radicci, V.; Wood, J. S.; Zhukova, V.; Bandurin, D.; Bolton, T.; Kaadze, K.; Kahl, W. E.; Maravin, Y.; Onoprienko, D.; Sidwell, R.; Wan, Z.; Dahmes, B.; Gronberg, J.; Hollar, J.; Lange, D.; Wright, D.; Wuest, C. R.; Baden, D.; Bard, R.; Eno, S. C.; Ferencek, D.; Hadley, N. J.; Kellogg, R. G.; Kirn, M.; Kunori, S.; Lockner, E.; Ratnikov, F.; Santanastasio, F.; Skuja, A.; Toole, T.; Wang, L.; Wetstein, M.; Alver, B.; Ballintijn, M.; Bauer, G.; Busza, W.; Gomez Ceballos, G.; Hahn, K. A.; Harris, P.; Klute, M.; Kravchenko, I.; Li, W.; Loizides, C.; Ma, T.; Nahn, S.; Paus, C.; Pavlon, S.; Piedra Gomez, J.; Roland, C.; Roland, G.; Rudolph, M.; Stephans, G.; Sumorok, K.; Vaurynovich, S.; Wenger, E. A.; Wyslouch, B.; Bailleux, D.; Cooper, S.; Cushman, P.; DeBenedetti, A.; Dolgopolov, A.; Dudero, P. R.; Egeland, R.; Franzoni, G.; Gilbert, W. J.; Gong, D.; Grahl, J.; Haupt, J.; Klapoetke, K.; Kronkvist, I.; Kubota, Y.; Mans, J.; Rusack, R.; Sengupta, S.; Sherwood, B.; Singovsky, A.; Vikas, P.; Zhang, J.; Booke, M.; Cremaldi, L. M.; Godang, R.; Kroeger, R.; Reep, M.; Reidy, J.; Sanders, D. A.; Sonnek, P.; Summers, D.; Watkins, S.; Bloom, K.; Bockelman, B.; Claes, D. R.; Dominguez, A.; Eads, M.; Furukawa, M.; Keller, J.; Kelly, T.; Lundstedt, C.; Malik, S.; Snow, G. R.; Swanson, D.; Ecklund, K. M.; Iashvili, I.; Kharchilava, A.; Kumar, A.; Strang, M.; Alverson, G.; Barberis, E.; Boeriu, O.; Eulisse, G.; McCauley, T.; Musienko, Y.; Muzaffar, S.; Osborne, I.; Reucroft, S.; Swain, J.; Taylor, L.; Tuura, L.; Gobbi, B.; Kubantsev, M.; Kubik, A.; Ofierzynski, R. A.; Schmitt, M.; Spencer, E.; Stoynev, S.; Szleper, M.; Velasco, M.; Won, S.; Andert, K.; Baumbaugh, B.; Beiersdorf, B. A.; Castle, L.; Chorny, J.; Goussiou, A.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kolberg, T.; Marchant, J.; Marinelli, N.; McKenna, M.; Ruchti, R.; Vigneault, M.; Wayne, M.; Wiand, D.; Bylsma, B.; Durkin, L. S.; Gilmore, J.; Gu, J.; Killewald, P.; Ling, T. Y.; Rush, C. J.; Sehgal, V.; Williams, G.; Adam, N.; Chidzik, S.; Denes, P.; Elmer, P.; Garmash, A.; Gerbaudo, D.; Halyo, V.; Jones, J.; Marlow, D.; Olsen, J.; Piroué, P.; Stickland, D.; Tully, C.; Werner, J. S.; Wildish, T.; Wynhoff, S.; Xie, Z.; Huang, X. T.; Lopez, A.; Mendez, H.; Ramirez Vargas, J. E.; Zatserklyaniy, A.; Apresyan, A.; Arndt, K.; Barnes, V. E.; Bolla, G.; Bortoletto, D.; Bujak, A.; Everett, A.; Fahling, M.; Garfinkel, A. F.; Gutay, L.; Ippolito, N.; Kozhevnikov, Y.; Laasanen, A. T.; Liu, C.; Maroussov, V.; Medved, S.; Merkel, P.; Miller, D. H.; Miyamoto, J.; Neumeister, N.; Pompos, A.; Roy, A.; Sedov, A.; Shipsey, I.; Cuplov, V.; Parashar, N.; Bargassa, P.; Lee, S. J.; Liu, J. H.; Maronde, D.; Matveev, M.; Nussbaum, T.; Padley, B. P.; Roberts, J.; Tumanov, A.; Bodek, A.; Budd, H.; Cammin, J.; Chung, Y. S.; DeBarbaro, P.; Demina, R.; Ginther, G.; Gotra, Y.; Korjenevski, S.; Miner, D. C.; Sakumoto, W.; Slattery, P.; Zielinski, M.; Bhatti, A.; Demortier, L.; Goulianos, K.; Hatakeyama, K.; Mesropian, C.; Bartz, E.; Chuang, S. H.; Doroshenko, J.; Halkiadakis, E.; Jacques, P. F.; Khits, D.; Lath, A.; Macpherson, A.; Plano, R.; Rose, K.; Schnetzer, S.; Somalwar, S.; Stone, R.; Watts, T. L.; Cerizza, G.; Hollingsworth, M.; Lazoflores, J.; Ragghianti, G.; Spanier, S.; York, A.; Aurisano, A.; Golyash, A.; Kamon, T.; Nguyen, C. N.; Pivarski, J.; Safonov, A.; Toback, D.; Weinberger, M.; Akchurin, N.; Berntzon, L.; Carrell, K. W.; Gumus, K.; Jeong, C.; Kim, H.; Lee, S. W.; McGonagill, B. G.; Roh, Y.; Sill, A.; Spezziga, M.; Thomas, R.; Volobouev, I.; Washington, E.; Wigmans, R.; Yazgan, E.; Bapty, T.; Engh, D.; Florez, C.; Johns, W.; Keskinpala, T.; Luiggi Lopez, E.; Neema, S.; Nordstrom, S.; Pathak, S.; Sheldon, P.; Andelin, D.; Arenton, M. W.; Balazs, M.; Buehler, M.; Conetti, S.; Cox, B.; Hirosky, R.; Humphrey, M.; Imlay, R.; Ledovskoy, A.; Phillips, D., II; Powell, H.; Ronquest, M.; Yohay, R.; Anderson, M.; Baek, Y. W.; Bellinger, J. N.; Bradley, D.; Cannarsa, P.; Carlsmith, D.; Crotty, I.; Dasu, S.; Feyzi, F.; Gorski, T.; Gray, L.; Grogg, K. S.; Grothe, M.; Jaworski, M.; Klabbers, P.; Klukas, J.; Lanaro, A.; Lazaridis, C.; Leonard, J.; Loveless, R.; Magrans de Abril, M.; Mohapatra, A.; Ott, G.; Smith, W. H.; Weinberg, M.; Wenman, D.; Atoian, G. S.; Dhawan, S.; Issakov, V.; Neal, H.; Poblaguev, A.; Zeller, M. E.; Abdullaeva, G.; Avezov, A.; Fazylov, M. I.; Gasanov, E. M.; Khugaev, A.; Koblik, Y. N.; Nishonov, M.; Olimov, K.; Umaraliev, A.; Yuldashev, B. S.

2008-08-01

The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 1034 cm-2 s-1 (1027 cm-2 s-1). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4π solid angle. Forward sampling calorimeters extend the pseudorapidity coverage to high values (|η| <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.

Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy.

PubMed

Saeidpour, S; Lohan, S B; Anske, M; Unbehauen, M; Fleige, E; Haag, R; Meinke, M C; Bittl, R; Teutloff, C

2017-07-01

The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of chronic mild stress on rats selectively bred for behavior related to bipolar disorder and depression.

PubMed

Murray, Ryan; Boss-Williams, Katherine A; Weiss, Jay M

2013-07-02

To test the possibility that chronic mild stress (CMS) might be unreliable in producing its often-intended outcome (i.e., decreased preference for sucrose, hypothesized to represent depression-relevant anhedonia) because it is typically applied to "normal" rats, a CMS procedure was applied to rats that may possess genetic susceptibility to affective disorders, having had been selectively-bred to show behavior indicative of such disorders. These rat lines were: Hyperactive (HYPER) rats, which show characteristics of bipolar disorder, Swim-test Susceptible (SUS) and Swim-test Resistant (RES) rats, being susceptible or resistant to effects of stress in the swim test, Swim High-active (SwHi) and Swim Low-active (SwLo) rats, which innately show high or low activity in the swim test. These selectively-bred lines were compared to normal, non-selectively bred (NS) rats. During CMS, HYPER rats, both females and males, as well as RES and SwHi rats, showed reduced consumption of a palatable 2% sucrose solution, and reduced preference for sucrose (vs. water) in comparison to non-stressed rats (no CMS) of the same lines. In contrast, CMS produced no decrease in sucrose consumption or in preference for sucrose in normal NS rats, and actually a caused a slight increase in sucrose consumption and preference in male NS rats. Other measures that indicate depression - food intake and motor activity in the home cage - were also assessed. SwLo and SwHi showed greater sensitivity to having their home-cage ambulatory activity reduced by CMS than did NS rats, but no other such differences relative to NS rats were seen for these other measures; thus, changes in sucrose intake or preference could not be explained by a change in caloric intake. These results suggest that the genetic attributes of animals can influence the outcome of CMS, and that the application of CMS to normal, non-selected rats may account, at least in part, for the unreliability of CMS in decreasing consumption of palatable substances and decreasing preference for such substances. Copyright © 2013. Published by Elsevier Inc.

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.

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.

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.

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

Sequence optimization to reduce velocity offsets in cardiovascular magnetic resonance volume flow quantification - A multi-vendor study

PubMed Central

2011-01-01

Purpose Eddy current induced velocity offsets are of concern for accuracy in cardiovascular magnetic resonance (CMR) volume flow quantification. However, currently known theoretical aspects of eddy current behavior have not led to effective guidelines for the optimization of flow quantification sequences. This study is aimed at identifying correlations between protocol parameters and the resulting velocity error in clinical CMR flow measurements in a multi-vendor study. Methods Nine 1.5T scanners of three different types/vendors were studied. Measurements were performed on a large stationary phantom. Starting from a clinical breath-hold flow protocol, several protocol parameters were varied. Acquisitions were made in three clinically relevant orientations. Additionally, a time delay between the bipolar gradient and read-out, asymmetric versus symmetric velocity encoding, and gradient amplitude and slew rate were studied in adapted sequences as exploratory measurements beyond the protocol. Image analysis determined the worst-case offset for a typical great-vessel flow measurement. Results The results showed a great variation in offset behavior among scanners (standard deviation among samples of 0.3, 0.4, and 0.9 cm/s for the three different scanner types), even for small changes in the protocol. Considering the absolute values, none of the tested protocol settings consistently reduced the velocity offsets below the critical level of 0.6 cm/s neither for all three orientations nor for all three scanner types. Using multilevel linear model analysis, oblique aortic and pulmonary slices showed systematic higher offsets than the transverse aortic slices (oblique aortic 0.6 cm/s, and pulmonary 1.8 cm/s higher than transverse aortic). The exploratory measurements beyond the protocol yielded some new leads for further sequence development towards reduction of velocity offsets; however those protocols were not always compatible with the time-constraints of breath-hold imaging and flow-related artefacts. Conclusions This study showed that with current systems there was no generic protocol which resulted into acceptable flow offset values. Protocol optimization would have to be performed on a per scanner and per protocol basis. Proper optimization might make accurate (transverse) aortic flow quantification possible for most scanners. Pulmonary flow quantification would still need further (offline) correction. PMID:21388521

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.

Increasing Testing Efficiency through the Development of an IT-Based Adaptive Testing Tool for Competency Measurement

ERIC Educational Resources Information Center

Kleinhans, Janne; Schumann, Matthias

2015-01-01

Purpose: This paper investigates the potential of computerized adaptive testing for CMs to reduce test time. In the context of education and training, competency measurement (CM) is a central challenge in competency management. For complex CMs, a compromise must be addressed between the time available and the quality of the measurements.…

Magnetic booster fast ignition macron accelerator

NASA Astrophysics Data System (ADS)

Winterberg, F.

2006-11-01

A new fast ignition scheme was recently proposed where the ignition is done by the impact of a small solid projectile accelerated to velocities in excess of 108cm/s, with the acceleration done in two steps: first, by laser ablation of a flyer plate, and second by injecting the flyer plate into a conical duct. The two principal difficulties of this scheme are as follows: first, the required large mass ratio for the laser ablation rocket propelled flyer plate, and second, the Rayleigh-Taylor instability of the flyer plate during its implosive compression in the conical duct. To overcome these difficulties, it is suggested to accelerate a projectile by a magnetic fusion booster stage, made up of a dense, wall-confined magnetized plasma brought to thermonuclear temperatures. After ignition, this plasma undergoes a thermonuclear excursion greatly increasing its pressure, resulting in the explosion of a weakened segment of the wall, with the segment becoming a fast moving projectile. The maximum velocity this projectile can reach is the velocity of sound of the booster stage plasma, which at a temperature of 108K is of the order 108cm/s.

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

PubMed

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

2016-06-06

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

Particle-flow reconstruction and global event description with the CMS detector

DOE PAGES

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

2017-10-06

The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMSmore » performance for jet and hadronic tau decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. In conclusion, the data collected by CMS at a centre-of-mass energy of 8 TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.« less

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

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

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

1999-04-13

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

Particle-flow reconstruction and global event description with the CMS detector

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

Sirunyan, A.M.; et al.

2017-10-06

The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMSmore » performance for jet and hadronic tau decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. The data collected by CMS at a centre-of-mass energy of 8 TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.« less

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.

Spin valve-like magnetic tunnel diode exhibiting giant positive junction magnetoresistance at low temperature in Co2MnSi/SiO2/p-Si heterostructure

NASA Astrophysics Data System (ADS)

Maji, Nilay; Kar, Uddipta; Nath, T. K.

2018-02-01

The rectifying magnetic tunnel diode has been fabricated by growing Co2MnSi (CMS) Heusler alloy film carefully on a properly cleaned p-Si (100) substrate with the help of electron beam physical vapor deposition technique and its structural, electrical and magnetic properties have been experimentally investigated in details. The electronic- and magneto-transport properties at various isothermal conditions have been studied in the temperature regime of 78-300 K. The current-voltage ( I- V) characteristics of the junction show an excellent rectifying magnetic tunnel diode-like behavior throughout that temperature regime. The current ( I) across the junction has been found to decrease with the application of a magnetic field parallel to the plane of the CMS film clearly indicating positive junction magnetoresistance (JMR) of the heterostructure. When forward dc bias is applied to the heterostructure, the I- V characteristics are highly influenced on turning on the field B = 0.5 T at 78 K, and the forward current reduces abruptly (99.2% current reduction at 3 V) which is nearly equal to the order of the magnitude of the current observed in the reverse bias. Hence, our Co2MnSi/SiO2/p-Si heterostructure can perform in off ( I off)/on ( I on) states with the application of non-zero/zero magnetic field like a spin valve at low temperature (78 K).

Susceptibility of a potential animal model for pathological anxiety to chronic mild stress.

PubMed

Salomons, Amber R; Kortleve, Tessa; Reinders, Niels R; Kirchhoff, Susanne; Arndt, Saskia S; Ohl, Frauke

2010-06-19

When anxiety-related behaviour in animals appears to lack adaptive value, it might be defined as pathological. Adaptive behaviour can be assessed for example by changes in behavioural responses over time, i.e. habituation. Thus, non-adaptive anxiety would be reflected by a lack of habituation. Recently, we found that 129P3/J mice are characterised by non-adaptive avoidance behaviour after repeated test exposure. The present study was aimed at investigating the sensitivity of the behavioural profile of these animals to exposure to a chronic mild stress (CMS) paradigm followed by repeated exposure to the modified hole board test. If the behavioural profile of 129P3/J mice mirrors pathological anxiety, their behavioural habituation under repeated test exposure conditions should be affected by CMS treatment. The results confirm the profound lack of habituation with respect to anxiety-related behaviour in both control and CMS treated mice. Additionally, CMS treated animals revealed a lower exploratory behaviour, reduced locomotor activity and increased arousal-related behaviour over time when compared to control individuals, proving an extension of their impaired habituation behaviour. Although no effects of CMS treatment on plasma corticosterone levels were found, higher immediate early gene expression in the bed nucleus of the stria terminalis and the ventrolateral periaqueductal grey in CMS treated mice indicated that 129P3/J mice are susceptible to the negative effects of CMS treatment at both the behavioural and the functional level. These results support the hypothesis that 129P3/J mice might be an interesting model for pathological anxiety. Copyright 2010 Elsevier B.V. All rights reserved.

Experimental Verification of Material Flammability in Space

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

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.

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.

Antidepressant, anxiolytic and procognitive effects of rivastigmine and donepezil in the chronic mild stress model in rats.

PubMed

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Willner, Paul

2016-04-01

The treatment of depression in old age is complicated by frequent co-morbidity with cognitive impairment. Anti-dementia drugs have some efficacy to improve cognitive performance and there is an inconsistent literature regarding the effect of such drugs on depressive symptoms. Here, we have investigated whether anti-dementia drugs would have antidepressant-like and pro-cognitive effects in a well-validated animal model of depression and cognitive impairment, chronic mild stress (CMS). Rats were subjected to CMS for a total of 8 weeks. After 2 weeks, subgroups of stressed and non-stressed animals were treated daily, for 5 weeks followed by 1 week of drug withdrawal, with vehicle, imipramine (10 mg/kg), rivastigmine (2 mg/kg), donepezil (0.3 mg/kg) or memantine (5 mg/kg). Sucrose intake was tested weekly, and animals were also tested in the elevated plus maze (at week 7) and in an object recognition task (at weeks 7 and 8). CMS decreased sucrose intake, had an anxiogenic effect in the elevated plus maze, and impaired performance in the object recognition test. Imipramine, rivastigmine and donepezil normalized performance in all three tests. Memantine had anxiolytic and pro-cognitive effects, but did not reverse CMS-induced anhedonia. The fact that all three anti-dementia drugs reversed CMS-induced cognitive impairment and that cholinesterase inhibitors, but not memantine, have antidepressant-like effects in this model suggest that different mechanisms may underlie CMS-induced anhedonia and cognitive impairment. We discuss the clinical implications of these findings.

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.

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.

Magnetic field effect on charmonium formation in high energy nuclear collisions

DOE PAGES

Guo, Xingyu; Shi, Shuzhe; Xu, Nu; ...

2015-10-23

It is important to understand the strong external magnetic field generated at the very beginning of heavy ion collisions. We study the effect of the magnetic field on the anisotropic charmonium formation in Pb + Pb collisions at the LHC energy. The time dependent Schrödinger equation is employed to describe the motion ofmore » $$c\\bar{c}$$ pairs. We compare our model prediction of the non-collective anisotropic parameter v 2 of J/ψ with CMS data at high transverse momentum.« less

47 CFR 10.350 - CMAS testing requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... maintenance windows. (3) A Participating CMS Provider may forego an RMT if the RMT is pre-empted by actual... Gateway Administrator using a defined test message. Real event codes or alert messages shall not be used... automated log of RMT messages received by the CMS Provider Gateway from the Federal Alert Gateway. (b...

47 CFR 10.350 - CMAS Testing requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... maintenance windows. (3) A Participating CMS Provider may forego an RMT if the RMT is pre-empted by actual... Gateway Administrator using a defined test message. Real event codes or alert messages shall not be used... automated log of RMT messages received by the CMS Provider Gateway from the Federal Alert Gateway. (b...

Prototypes and system test stands for the Phase 1 upgrade of the CMS pixel detector

DOE PAGES

Hasegawa, S.

2016-04-23

The CMS pixel phase-1 upgrade project replaces the current pixel detector with an upgraded system with faster readout electronics during the extended year-end technical stop of 2016/2017. New electronics prototypes for the system have been developed, and tests in a realistic environment for a comprehensive evaluation are needed. A full readout test stand with either the same hardware as used in the current CMS pixel detector or the latest prototypes of upgrade electronics has been built. The setup enables the observation and investigation of a jitter increase in the data line associated with trigger rate increases. This effect is duemore » to the way in which the clock and trigger distribution is implemented in CMS. A new prototype of the electronics with a PLL based on a voltage controlled quartz crystal oscillator (QPLL), which works as jitter filter, in the clock distribution path was produced. With the test stand, it was confirmed that the jitter increase is not seen with the prototype, and also good performance was confirmed at the expected detector operation temperature ($-$20 °C).« less

Increase in Testing Efficiency through the Development of an IT-Based Adaptive Testing Tool for Competency Measurement Applied to a Health Worker Training Test Case

ERIC Educational Resources Information Center

Kleinhans, Janne; Schumann, Matthias

2015-01-01

In the context of education and training, competency measurement (CM) is a central challenge in competency management. For complex CMs, a compromise must be addressed between the time available and the number of dimensions to be measured or the quality of the measurements. Increasing the efficiency of existing tests for CMs therefore poses a key…

Test of the wire ageing induced by radiation for the CMS barrel muon chambers

NASA Astrophysics Data System (ADS)

Conti, E.; Gasparini, F.

2001-06-01

We have carried out laboratory tests to measure the ageing of a wire tube due to pollutants outgassed by various materials. The tested materials are those used in the barrel muon drift tubes of the CMS experiment at LHC. An X-ray gun irradiated the test tube to accelerate the ageing process. No ageing effect has been measured for a period equivalent to 10 years of operation at LHC.

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

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

PubMed

Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2005-09-08

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression.

PubMed

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Willner, Paul

2017-02-01

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

Constructing a 4-TESLA Large Thin Solenoid at the Limit of what can BE Safely Operated

NASA Astrophysics Data System (ADS)

Hervé, A.

The 4-tesla, 6 m free bore CMS solenoid has been successfully tested, operated and mapped at CERN during the autumn of 2006 in a surface hall and fully recommissioned in the underground experimental area in the autumn of 2008. The conceptual design started in 1990, the R&D studies in 1993, and the construction was approved in 1997. At the time the main parameters of this project were considered beyond what was thought possible as, in particular, the total stored magnetic energy reaches 2.6 GJ for a specific magnetic energy density exceeding 11 kJ/kg of cold mass. During this period, the international design and construction team had to make several important technical choices, particularly mechanical ones, to maximize the chances of reaching the nominal induction of 4 T. These design choices are explained and critically reviewed in the light of what is presently known to determine if better solutions would be possible today for constructing a new large high-field thin solenoid for a future detector magnet.

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.…

Hyperoside protects against chronic mild stress-induced learning and memory deficits.

PubMed

Gong, Yeli; Yang, Youhua; Chen, Xiaoqing; Yang, Min; Huang, Dan; Yang, Rong; Zhou, Lianying; Li, Changlei; Xiong, Qiuju; Xiong, Zhe

2017-07-01

Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Young-Adult Male Rats' Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors.

PubMed

José Jaime, Herrera-Pérez; Venus, Benítez-Coronel; Graciela, Jiménez-Rubio; Tania, Hernández-Hernández Olivia; Lucía, Martínez-Mota

2016-01-01

In a previous study, we found that chronic mild stress (CMS) paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal's vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals' body weight and sucrose preference (indicator of anhedonia) were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests); meanwhile, others were used to measure serum corticosterone. We found that CMS (1) did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2) decreased body weight gain; and (3) increased the rat's entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats' vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors.

Young-Adult Male Rats' Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors

PubMed Central

José Jaime, Herrera-Pérez; Venus, Benítez-Coronel; Graciela, Jiménez-Rubio; Tania, Hernández-Hernández Olivia

2016-01-01

In a previous study, we found that chronic mild stress (CMS) paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal's vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals' body weight and sucrose preference (indicator of anhedonia) were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests); meanwhile, others were used to measure serum corticosterone. We found that CMS (1) did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2) decreased body weight gain; and (3) increased the rat's entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats' vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors. PMID:27433469

Rectifying magnetic tunnel diode like behavior in Co2MnSi/ZnO/p-Si heterostructure

NASA Astrophysics Data System (ADS)

Maji, Nilay; Nath, T. K.

2018-04-01

The rectifying magnetic tunnel diode like behavior has been observed in Co2MnSi/ZnO/p-Si heterostructure. At first an ultra thin layer of ZnO has been deposited on p-Si (100) substrate with the help of pulsed laser deposition (PLD). After that a highly spin-polarized Heusler alloy Co2MnSi (CMS) film (250 nm) has been grown on ZnO/p-Si using electron beam physical vapor deposition technique. The phase purity of the sample has been confirmed through high resolution X-Ray diffraction technique. The electrical transport properties have been investigated at various isothermal conditions in the temperature range of 77-300 K. The current-voltage characteristics exhibit an excellent rectifying tunnel diode like behavior throughout the temperature regime. The current (I) across the junction has been found to decrease with the application of an external magnetic field parallel to the plane of the CMS film clearly indicating positive junction magnetoresistance (JMR) of the heterostructure. The magnetic field dependent JMR behavior of our heterostructure has been investigated in the same temperature range. Our heterostructure clearly demonstrates a giant positive JMR at 78 K (˜264%) and it starts decreasing with increasing temperature. If we compare our results with earlier reported results on other heterostructures, it can be seen that the JMR value for our heterojunction saturates at a much lower external magnetic field, thus creating it a better alternative for spin tunnel diodes in upcoming spintronics device applications.

Mangiferin inhibits hippocampal NLRP3 inflammasome and exerts antidepressant effects in a chronic mild stress mice model.

PubMed

Cao, Changfu; Su, Meiqing; Zhou, Feng

2017-08-01

A growing body of evidence suggests that inflammation may contribute toward the development of major depressive disorder. Mangiferin, a glucosylxanthone from Mangifera indica, exerts a number of biological actions, including anti-inflammatory effects. Although mangiferin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study investigated the effects of mangiferin on behavioral changes and inflammatory responses induced by chronic mild stress (CMS) in mice. We found that treatment with mangiferin for 3 weeks significantly increased the body weight of mice and ameliorated CMS-induced behavioral abnormalities by increasing sucrose consumption, improving locomotor activities, and decreasing the immobility time in the forced-swimming test and tail-suspension test. It also suppressed increased serum corticosterone levels in CMS mice. In response to CMS induction, the NLR family, pyrin domain containing 3 (NLRP3) inflammasome was activated and interleukin (IL)-1β and IL-18 levels were increased in the mouse hippocampus. Mangiferin treatment downregulated the expression of NLRP3, the adaptor protein ASC, and caspase-1, which subsequently reduced the production of IL-1β and IL-18 in CMS mice. In sum, our results indicate that mangiferin exerts antidepressant-like effects in CMS model, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression.

Dendritic Core-Multishell Nanocarriers in Murine Models of Healthy and Atopic Skin.

PubMed

Radbruch, Moritz; Pischon, Hannah; Ostrowski, Anja; Volz, Pierre; Brodwolf, Robert; Neumann, Falko; Unbehauen, Michael; Kleuser, Burkhard; Haag, Rainer; Ma, Nan; Alexiev, Ulrike; Mundhenk, Lars; Gruber, Achim D

2017-12-01

Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e.g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection.Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis.Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin.

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.

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

PubMed

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

2018-01-01

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

Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

PubMed

Delis, Foteini; Thanos, Panayotis K; Rombola, Christina; Rosko, Lauren; Grandy, David; Wang, Gene-Jack; Volkow, Nora D

2013-02-01

Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

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...

Magnolol abrogates chronic mild stress-induced depressive-like behaviors by inhibiting neuroinflammation and oxidative stress in the prefrontal cortex of mice.

PubMed

Cheng, Jie; Dong, Shuqi; Yi, Litao; Geng, Di; Liu, Qing

2018-06-01

Magnolol, the main constituent of Magnolia officinalis, has been shown to produce antidepressant-like effect in rodents. Growing evidence shows that neuroinflammation, oxidative stress and neuroendocrine contribute to the pathogenesis of major depression. Here, the aim of this present study was to determine whether magnolol affected these systems in mice exposed to chronic mild stress (CMS). The ameliorative effect of magnolol on depressive-like symptoms was investigated through behavioral tests, including the classical sucrose preference and forced swimming tests. The behavioral evaluation showed that magnolol reversed the depressive-like deficits both in sucrose preference test and forced swimming test. The elevation of prefrontal cortex pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was decreased by magnolol. Consistently, the microglia activation by CMS was also alleviated by magnolol. In addition, the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induced by CMS was attenuated by magnolol. Moreover, the increased lipid peroxidation such as malonaldehyde (MDA) and decreased antioxidant defense enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) induced by CMS were also reversed by magnolol. These findings suggest that administration of magnolol could alleviate depressive-like behaviors in CMS mice that are mediated by suppressing neuroinflammation and oxidative stress in the prefrontal cortex. Copyright © 2018 Elsevier B.V. All rights reserved.

Search for effective spin injection heterostructures based on half-metal Heusler alloys/gallium arsenide semiconductors: A theoretical investigation

NASA Astrophysics Data System (ADS)

Sivakumar, Chockalingam

Efficient electrical spin injection from half-metal (HM) electrodes into semiconducting (SC) channel material is a desirable aspect in spintronics, but a challenging one. Half-metals based on the Heusler alloy family are promising candidates as spin sources due to their compatibility with compound SCs, and very high Curie temperatures. Numerous efforts were made in the past two decades to grow atomically abrupt interfaces between HM_Heusler and SC heterostructures. However, diffusion of magnetic impurities into the semiconductor, defects and disorder near the interface, and formation of reacted phases were great challenges. A number of theoretical efforts were undertaken to understand the role of such material defects in destroying the half-metallicity and also to propose promising half-metal/SC heterostructures based on first principles. This dissertation summarizes the investigations undertaken to decode the complexity of, and to understand the various physical properties of, a number of real-world Heusler/SC heterostructure samples, based on the ab initio density functional theory (DFT) approach. In addition, it summarizes various results from the first principles-based search for promising half-metal/SC heterostructures. First, I present results from DFT-based predictive models of actual Co 2MnSi (CMS)/GaAs heterostructures grown in (001) texture. I investigate the physical, chemical, electronic, and magnetic properties to understand the complexity of these structures and to pinpoint the origin of interfacial effects, when present. Based on the investigations of such models, I discuss the utility of those actual samples in spintronic applications. Next, I summarise the results from an ab initio DFT-based survey of 6 half-Heusler half-metal/GaAs heterostructure models in (110) texture, since compound semiconductors such as GaAs have very long spin lifetime in (110) layering. I show 3 half-Heusler alloys (CoVAs, NiMnAs, and RhFeGe), that when interfaced with GaAs(110), fully preserve the half-metallicity at the interface. Finally, I show the advantages of inserting half-Heusler SCs, particularly CoTiAs and CoTiSb, as spacers in between CMS/GaAs systems in (110) layering. Based on DFT calculations, I show that CoTiAs is a promising spacer that could enhance the perpendicular magnetic anisotropy in CMS, while preserving the important half-metallic character at the heterojunctions between CMS/CoTiAs/GaAs(110). This spacer could also serve to prevent in-diffusion of magnetic impurities into the channel material.

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

PubMed

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

2017-01-01

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

Results from a first production of enhanced Silicon Sensor Test Structures produced by ITE Warsaw

NASA Astrophysics Data System (ADS)

Bergauer, T.; Dragicevic, M.; Frey, M.; Grabiec, P.; Grodner, M.; Hänsel, S.; Hartmann, F.; Hoffmann, K.-H.; Hrubec, J.; Krammer, M.; Kucharski, K.; Macchiolo, A.; Marczewski, J.

2009-01-01

Monitoring the manufacturing process of silicon sensors is essential to ensure stable quality of the produced detectors. During the CMS silicon sensor production we were utilising small Test Structures (TS) incorporated on the cut-away of the wafers to measure certain process-relevant parameters. Experience from the CMS production and quality assurance led to enhancements of these TS. Another important application of TS is the commissioning of new vendors. The measurements provide us with a good understanding of the capabilities of a vendor's process. A first batch of the new TS was produced at the Institute of Electron Technology in Warsaw Poland. We will first review the improvements to the original CMS test structures and then discuss a selection of important measurements performed on this first batch.

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

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

The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMSmore » performance for jet and hadronic tau decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. In conclusion, the data collected by CMS at a centre-of-mass energy of 8 TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.« less

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

PubMed Central

Lundy, Scott D.; Zhu, Wei-Zhong

2013-01-01

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

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.

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.

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.

Evaluation of radar activated changeable message sign for work zone speed control.

DOT National Transportation Integrated Search

2002-01-01

The Maine Department of Transportation recently tested new equipment designed to help reduce the : incidence of speeding in construction work zones. The project utilized a radar-activated, trailer mounted, : changeable message sign (CMS). The CMS spe...

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.

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...

A new data acquisition system for the CMS Phase 1 pixel detector

NASA Astrophysics Data System (ADS)

Kornmayer, A.

2016-12-01

A new pixel detector will be installed in the CMS experiment during the extended technical stop of the LHC at the beginning of 2017. The new pixel detector, built from four layers in the barrel region and three layers on each end of the forward region, is equipped with upgraded front-end readout electronics, specifically designed to handle the high particle hit rates created in the LHC environment. The DAQ back-end was entirely redesigned to handle the increased number of readout channels, the higher data rates per channel and the new digital data format. Based entirely on the microTCA standard, new front-end controller (FEC) and front-end driver (FED) cards have been developed, prototyped and produced with custom optical link mezzanines mounted on the FC7 AMC and custom firmware. At the same time as the new detector is being assembled, the DAQ system is set up and its integration into the CMS central DAQ system tested by running the pilot blade detector already installed in CMS. This work describes the DAQ system, integration tests and gives an outline for the activities up to commissioning the final system at CMS in 2017.

Integration and validation testing for PhEDEx, DBS and DAS with the PhEDEx LifeCycle agent

NASA Astrophysics Data System (ADS)

Boeser, C.; Chwalek, T.; Giffels, M.; Kuznetsov, V.; Wildish, T.

2014-06-01

The ever-increasing amount of data handled by the CMS dataflow and workflow management tools poses new challenges for cross-validation among different systems within CMS experiment at LHC. To approach this problem we developed an integration test suite based on the LifeCycle agent, a tool originally conceived for stress-testing new releases of PhEDEx, the CMS data-placement tool. The LifeCycle agent provides a framework for customising the test workflow in arbitrary ways, and can scale to levels of activity well beyond those seen in normal running. This means we can run realistic performance tests at scales not likely to be seen by the experiment for some years, or with custom topologies to examine particular situations that may cause concern some time in the future. The LifeCycle agent has recently been enhanced to become a general purpose integration and validation testing tool for major CMS services. It allows cross-system integration tests of all three components to be performed in controlled environments, without interfering with production services. In this paper we discuss the design and implementation of the LifeCycle agent. We describe how it is used for small-scale debugging and validation tests, and how we extend that to large-scale tests of whole groups of sub-systems. We show how the LifeCycle agent can emulate the action of operators, physicists, or software agents external to the system under test, and how it can be scaled to large and complex systems.

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.

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.

First-principles study of spin-transfer torque in Co{sub 2}MnSi/Al/Co{sub 2}MnSi spin-valve

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

Tang, Ling, E-mail: lingtang@zjut.edu.cn; Yang, Zejin, E-mail: zejinyang@zjut.edu.cn

The spin-transfer torque (STT) in Co{sub 2}MnSi(CMS)/Al/Co{sub 2}MnSi spin-valve system with and without interfacial disorder is studied by a first-principles noncollinear wave-function-matching method. It is shown that in the case of clean interface the angular dependence of STT for CoCo/Al (the asymmetry parameter Λ≈4.5) is more skewed than that for MnSi/Al (Λ≈2.9), which suggests the clean CoCo/Al architecture is much more efficient for the application on radio frequency oscillation. We also find that even with interfacial disorder the spin-valve of half-metallic CMS still has a relatively large parameter Λ compared to that of conventional ferromagnet. In addition, for clean interfacemore » the in-plane torkance of MnSi/Al is about twice as large as that of CoCo/Al. However, as long as the degree of interfacial disorder is sufficiently large, the CoCo/Al and MnSi/Al will show approximately the same magnitude of in-plane torkance. Furthermore, our results demonstrate that CMS/Al/CMS system has very high efficiency of STT to switch the magnetic layer of spin-valve.« less

Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS).

PubMed

Chandrasekhar, Y; Ramya, E M; Navya, K; Phani Kumar, G; Anilakumar, K R

2017-02-01

Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i.p.) and TC (25, 50 and 100mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A study on size effect of carboxymethyl starch nanogel crosslinked by electron beam radiation

NASA Astrophysics Data System (ADS)

Binh, Doan; Pham Thi Thu Hong; Nguyen Ngoc Duy; Nguyen Thanh Duoc; Nguyen Nguyet Dieu

2012-07-01

The formation of carboxymethyl starch (CMS) nanogel with 50 nm less particle size was carried out through a radiation crosslinked process on the electron beam (EB) linear accelerator. Changes of intrinsic viscosities and weight averaged molecular weight in the CMS concentration, which ranged from 3 to 10 mg ml-1 in absorbed doses were investigated. There were some new peaks in the 1H NMR spectra of CMS nanogel compared with those of CMS polymer. These results were anticipated that the predominant intramolecular crosslinking of dilute CMS aqueous solution occurred while being exposed to a short intense pulse of ionizing radiation. Hydrodynamic radius (often called particle size, Rh) and distribution of particle size were measured by a dynamic light scattering technique. The radiation yield of intermolecular crosslinking of CMS solution was calculated from the expression of Gx (Charlesby, 1960; Jung-Chul, 2010). The influence of the "size effect" was demonstrated by testing culture of Lactobacillus bacteria on MRS agar culture medium containing CMS nanogel and polymer. Results showed that the number of Lactobacillus bacteria growing on nanogel containing culture medium is about 170 cfu/ml and on polymer containing culture medium is only 6 cfu/ml.

FDR Soil Moisture Sensor for Environmental Testing and Evaluation

NASA Astrophysics Data System (ADS)

Linmao, Ye; longqin, Xue; guangzhou, Zhang; haibo, Chen; likuai, Shi; zhigang, Wu; gouhe, Yu; yanbin, Wang; sujun, Niu; Jin, Ye; Qi, Jin

To test the affect of environmental stresses on a adaptability of soil moisture capacitance sensor(FDR) a number of stresses were induced including vibrational shock as well as temperature and humidity through the use of a CH-I constant humidity chamber with variable temperature. A Vibrational platform was used to exam the resistance and structural integrity of the sensor after vibrations simulating the process of using, transporting and handling the sensor. A Impactive trial platform was used to test the resistance and structural integrity of the sensor after enduring repeated mechanical shocks. An CH-I constant humidity chamber with high-low temperature was used to test the adaptability of sensor in different environments with high temperature, low temperature and constant humidity. Otherwise, scope of magnetic force line of sensor was also tested in this paper. Test show:the capacitance type soil moisture sensor spread a feeling machine to bear heat, high wet and low temperature, at bear impact and vibration experiment in pass an examination, is a kind of environment to adapt to ability very strong instrument;Spread a feeling machine moreover electric field strength function radius scope 7 cms.

An Advocate for Every Student at Millard Central Middle School

ERIC Educational Resources Information Center

Balkus, Beth

2006-01-01

Central Middle School, part of the Millard Public School District, is a grade six through eight urban school located in Omaha, Nebraska. Omaha has a metropolitan and surrounding suburban population of approximately one million. Along with approximately 800 students in traditional middle school teams, CMS also offers a Montessori mini-magnet and…

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.

Constructing a 4-Tesla Large Thin Solenoid at the Limit of what can BE Safely Operated

NASA Astrophysics Data System (ADS)

Hervé, A.

The 4-tesla, 6m free bore CMS solenoid has been successfully tested, operated and mapped at CERN during the autumn of 2006 in a surface hall and fully recommissioned in the underground experimental area in the autumn of 2008. The conceptual design started in 1990, the R&D studies in 1993, and the construction was approved in 1997. At the time the main parameters of this project were considered beyond what was thought possible as, in particular, the total stored magnetic energy reaches 2.6GJ for a specific magnetic energy density exceeding 11 kJ/kg of cold mass. During this period, the international design and construction team had to make several important technical choices, particularly mechanical ones, to maximize the chances of reaching the nominal induction of 4T. These design choices are explained and critically reviewed in the light of what is presently known to determine if better solutions would be possible today for constructing a new large high-field thin solenoid for a future detector magnet.

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.

Cuticular Membrane of Fuyu Persimmon Fruit Is Strengthened by Triterpenoid Nano-Fillers

PubMed Central

Tsubaki, Shuntaro; Sugimura, Kazuki; Teramoto, Yoshikuni; Yonemori, Keizo; Azuma, Jun-ichi

2013-01-01

The mechanical defensive performance of fruit cuticular membranes (CMs) is largely dependent on the molecular arrangement of their constituents. Here, we elucidated nano-sized interactions between cutin and triterpenoids in the cuticular matrix of Fuyu persimmon fruits ( Diospyros kaki Thunb. cv. Fuyu), focusing on the mechanical properties using a combination of polymer analyses. The fruit CMs of Fuyu were primarily composed of wax (34.7%), which was predominantly triterpenoids followed by higher aliphatic compounds, and cutin (48.4%), primarily consisting of 9,10-epoxy-18-hydroxyoctadecanoic acid and 9,10,18-trihydroxyoctadecanoic acid. Based on the tensile tests of the CM, the removal of wax lead to a considerable decrease in the maximum stress and elastic modulus accompanied by an increase in the maximum strain, indicating that wax is of significant importance for maintaining the mechanical strength of the CM. Wide-angle X-ray diffraction and relaxation time measurements using solid-state 13C nuclear magnetic resonance indicated that the triterpenoids in the cuticular matrix construct a nanocomposite at a mixing scale below 20-24 nm; however, the higher aliphatic compounds did not exhibit clear interactions with cutin. The results indicated that the triterpenoids in the cuticular matrix endow toughness to the CM by functioning as a nanofiller. PMID:24086493

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.

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

Experience in Grid Site Testing for ATLAS, CMS and LHCb with HammerCloud

NASA Astrophysics Data System (ADS)

Elmsheuser, Johannes; Medrano Llamas, Ramón; Legger, Federica; Sciabà, Andrea; Sciacca, Gianfranco; Úbeda García, Mario; van der Ster, Daniel

2012-12-01

Frequent validation and stress testing of the network, storage and CPU resources of a grid site is essential to achieve high performance and reliability. HammerCloud was previously introduced with the goals of enabling VO- and site-administrators to run such tests in an automated or on-demand manner. The ATLAS, CMS and LHCb experiments have all developed VO plugins for the service and have successfully integrated it into their grid operations infrastructures. This work will present the experience in running HammerCloud at full scale for more than 3 years and present solutions to the scalability issues faced by the service. First, we will show the particular challenges faced when integrating with CMS and LHCb offline computing, including customized dashboards to show site validation reports for the VOs and a new API to tightly integrate with the LHCbDIRAC Resource Status System. Next, a study of the automatic site exclusion component used by ATLAS will be presented along with results for tuning the exclusion policies. A study of the historical test results for ATLAS, CMS and LHCb will be presented, including comparisons between the experiments’ grid availabilities and a search for site-based or temporal failure correlations. Finally, we will look to future plans that will allow users to gain new insights into the test results; these include developments to allow increased testing concurrency, increased scale in the number of metrics recorded per test job (up to hundreds), and increased scale in the historical job information (up to many millions of jobs per VO).

One Year of FOS Measurements in CMS Experiment at CERN

NASA Astrophysics Data System (ADS)

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

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

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.

[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."

A simulation framework for the CMS Track Trigger electronics

NASA Astrophysics Data System (ADS)

Amstutz, C.; Magazzù, G.; Weber, M.; Palla, F.

2015-03-01

A simulation framework has been developed to test and characterize algorithms, architectures and hardware implementations of the vastly complex CMS Track Trigger for the high luminosity upgrade of the CMS experiment at the Large Hadron Collider in Geneva. High-level SystemC models of all system components have been developed to simulate a portion of the track trigger. The simulation of the system components together with input data from physics simulations allows evaluating figures of merit, like delays or bandwidths, under realistic conditions. The use of SystemC for high-level modelling allows co-simulation with models developed in Hardware Description Languages, e.g. VHDL or Verilog. Therefore, the simulation framework can also be used as a test bench for digital modules developed for the final system.

Mechanical design, fabrication, and test of biomimetic fish robot using LIPCA as artificial muscle

NASA Astrophysics Data System (ADS)

Wiguna, T.; Syaifuddin, M.; Park, Hoon C.; Heo, S.

2006-03-01

This paper presents a mechanical design, fabrication and test of biomimetic fish robot using the Lightweight Piezocomposite Curved Actuator (LIPCA). We have designed a mechanism for converting actuation of the LIPCA into caudal fin movement. This linkage mechanism consists of rack-pinion system and four-bar linkage. We also have tested four types of caudal fin in order to examine effect of different shape of caudal fin on thrust generation by tail beat. Subsequently, based on the caudal fin test, four caudal fins which resemble fish caudal fin shapes of ostraciiform, subcarangiform, carangiform and thunniform, respectively, are attached to the posterior part of the robotic fish. The swimming test using 300 V pp input with 1 Hz to 1.5 Hz frequency was conducted to investigate effect of changing tail beat frequency and shape of caudal fin on the swimming speed of the robotic fish. The maximum swimming speed was reached when the device was operated at its natural swimming frequency. At the natural swimming frequency 1 Hz, maximum swimming speeds of 1.632 cm/s, 1.776 cm/s, 1.612 cm/s and 1.51 cm/s were reached for ostraciiform-, subcarangiform-, carangiform- and thunniform-like caudal fins, respectively. Strouhal numbers, which are a measure of thrust efficiency, were calculated in order to examine thrust performance of the present biomimetic fish robot. We also approximated the net forward force of the robotic fish using momentum conservation principle.

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.

Autonomic arterial neuropathy in lower limbs.

PubMed

Ener, B K; Uçankale, H

2015-06-01

This prospective and controlled study was carried out to show the role of hyperperfusion due to decreased arterial resistance in patients with arterial neuropathy of lower limbs. Arterial Duplex color scanning and magnetic resonance imaging (MRI) angiography were made in 54 patients with lower limb venous stasis in which Pulsatility Index (PI) from pedal arteries by using CW Doppler was below cut off value of 5 as a confirmatory evidence of autonomic neuropathy and in 24 healthy subjects. PI was mean 2.79 ranged from 4.87 to 0.82 in patients. It was mean 9.38 between 5.43 and 15.25 in control subjects. PSV was found mean 44.52 cm/sec ranged from 26 to 74 cm/s in patients. It was found between 10 and 23 cm/sec with average 16.08 cm/s in healthy ones. In addition to venous duplex scanning findings, MRI angiography demonstrates arterial contrast enhancement, vascular blush, early venous filling and permanent venous dilatation in 16 patients (group 2) having PI below 3 with severe degrees of hyperperfusion. In this group, PI was mean 1.70 ranged from 2.46 to 0.82 and PSV was mean 61.19 cm/s, between 53 to 74 cm/s. Out of patients, 38 (group 1) had no pathological findings in MRI angiography and had PI>3 and <5. In this group, PI was mean 3.26, ranged from 4.87 to 2.55 and PSV was mean 37.5 cm/s, between 26 to 47 cm/s. In this trial, we observed that patients with arterial neuropathy in the leg (groups 1 and 2) had a significant increase in PSV and a decrease in PI values from foot arteries compared with that of the control group (P=0.001). A remarkable difference was found in parameters between patient groups (P=0.001). Finally, it can be said that lower limb hyperperfusion owing to arterial neuropathy in various degrees produce venous stasis and is also responsible for some venous abnormalities.

The Development of Chorus Motivation Scale (CMS) for Prospective Music Teacher

ERIC Educational Resources Information Center

Ozgul, Ilhan; Yigit, Nalan

2017-01-01

The purpose of this study was to develop a Chorus Motivation Scale (CMS) that is tested in terms of reliability and construct validity by determining the student perceptions of effective motivation strategies in Chorus training in Turkish Music Teacher Training Model. In order to develop a Chorus Motivation Scale, Questionnaire-Effective…

Neuropsychological function in children with primary complex motor stereotypies.

PubMed

Mahone, E Mark; Ryan, Matthew; Ferenc, Lisa; Morris-Berry, Christina; Singer, Harvey S

2014-10-01

Complex motor stereotypies (CMS) are patterned, repetitive, rhythmic, and involuntary movements that persist over time. They are divided into two subgroups dependent on the presence of other developmental problems: 'primary' (development is otherwise typical) or 'secondary' (associated with autism, intellectual disability, or sensory deficits). There are no currently published studies that examine neuropsychological function in children with primary CMS. This case-control study examines whether children with primary CMS manifest neurobehavioral deficits. Fifty-seven children with primary CMS (32 males, 25 females; mean age 6y 8mo, SD 2y 4mo, range 4-12y) with negative screens for autism and 57 comparison participants (32 males, 25 females; mean age 6y 6mo, SD 2y 1mo) completed neuropsychological assessments of IQ, reading ability, attention, language, and motor and executive functions. Parents completed ratings of their child's repetitive movement severity. The CMS group performed significantly less well than comparison participants on motor skills and IQ tests (both p<0.01), although IQ was consistently in the average range. One-third of the CMS group showed signs of developmental motor coordination difficulties. Parent report of stereotypy severity was significantly associated with parent report of inattention and executive dysfunction. Children with primary CMS were found to have largely intact neuropsychological profiles. Stereotypy severity appears to be associated with executive dysfunction. Although motor difficulties were observed in children with CMS, these were not correlated with parent report of symptom severity. © 2014 Mac Keith Press.

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

Radiation Hard Active Media R&D for CMS Hadron Endcap Calorimetry

NASA Astrophysics Data System (ADS)

Tiras, Emrah; CMS-HCAL Collaboration

2015-04-01

The High Luminosity LHC era imposes unprecedented radiation conditions on the CMS detectors targeting a factor of 5-10 higher than the LHC design luminosity. The CMS detectors will need to be upgraded in order to withstand these conditions yet maintain/improve the physics measurement capabilities. One of the upgrade options is reconstructing the CMS Endcap Calorimeters with a shashlik design electromagnetic section and replacing active media of the hadronic section with radiation-hard scintillation materials. In this context, we have studied various radiation-hard materials such as Polyethylene Naphthalate (PEN), Polyethylene Terephthalate (PET), HEM and quartz plates coated with various organic materials such as p-Terphenyl (pTp), Gallium doped Zinc Oxide (ZnO:Ga) and Anthracene. Here we discuss the related test beam activities, laboratory measurements and recent developments.

How the center for Medicare and Medicaid innovation should test accountable care organizations.

PubMed

Shortell, Stephen M; Casalino, Lawrence P; Fisher, Elliott S

2010-07-01

The Patient Protection and Affordable Care Act establishes a national voluntary program for accountable care organizations (ACOs) by January 2012 under the auspices of the Centers for Medicare and Medicaid Services (CMS). The act also creates a Center for Medicare and Medicaid Innovation in the CMS. We propose that the CMS allow flexibility and tiers in ACOs based on their specific circumstances, such as the degree to which they are or are not fully integrated systems. Further, we propose that the CMS assume responsibility for ACO provisions and develop an ordered system for learning how to create and sustain ACOs. Key steps would include setting specific performance goals, developing skills and tools that facilitate change, establishing measurement and accountability mechanisms, and supporting leadership development.

Synthesis and characterization of carbon microsphere for extinguishing sodium fire

NASA Astrophysics Data System (ADS)

Snehalatha, V.; Ponraju, D.; Nashine, B. K.; Chellapandi, P.

2013-06-01

In Sodium cooled Fast breeder Reactors (SFRs), accidental leakage of liquid sodium leads to sodium fire. Carbon microsphere is a promising and novel extinguishant for sodium fire since it possesses high thermal conductivity, chemical inertness and excellent flow characteristics. Low density Carbon microsphere (CMS) with high thermal stability was successfully synthesized from functionalized styrene divinyl benzene copolymer by carbonization under inert atmosphere. Protocol for stepwise carbonization was developed by optimizing heating rate and time of heating. The synthesized CMS was characterized by Densimeter, Scanning Electron Microscope (SEM), Fourier Transfer Infra-Red spectroscopy (FTIR), Thermogravimetry (TG), X-ray Diffraction (XRD) and RAMAN spectroscopy. CMS thus obtained was spherical in shape having diameters ranging between 60 to 80μm with narrow size distribution. The smooth surface of CMS ensures its free flow characteristics. The yield of carbonization process was about 38%. The performance of CMS was tested on small scale sodium. This paper describes the development of carbon microsphere for extinguishing sodium fire and its characteristics.

Proceedings of the Eleventh International Conference on Calorimetry in Particle Physics

NASA Astrophysics Data System (ADS)

Cecchi, Claudia

The Pamela silicon tungsten calorimeter / G. Zampa -- Design and development of a dense, fine grained silicon tungsten calorimeter with integrated electronics / D. Strom -- High resolution silicon detector for 1.2-3.1 eV (400-1000 nm) photons / D. Groom -- The KLEM high energy cosmic rays collector for the NUCLEON satellite mission / M. Merkin (contribution not received) -- The electromagnetic calorimeter of the Hera-b experiment / I. Matchikhilian -- The status of the ATLAS tile calorimeter / J. Mendes Saraiva -- Design and mass production of Scintillator Pad Detector (SPD) / Preshower (PS) detector for LHC-b experiment / E. Gushchin -- Study of new FNAL-NICADD extruded scintillator as active media of large EMCal of ALICE at LHC / O. Grachov -- The CMS hadron calorimeter / D. Karmgard (contribution not received) -- Test beam study of the KOPIO Shashlyk calorimeter prototype / A. Poblaguev -- The Shashlik electro-magnetic calorimeter for the LHCb experiment / S. Barsuk -- Quality of mass produced lead-tungstate crystals / R. Zhu -- Status of the CMS electromagnetic calorimeter / J. Fay -- Scintillation detectors for radiation-hard electromagnetic calorimeters / H. Loehner -- Energy, timing and two-photon invariant mass resolution of a 256-channel PBWO[symbol] calorimeter / M. Ippolitov -- A high performance hybrid electromagnetic calorimeter at Jefferson Lab / A. Gasparian -- CsI(Tl) calorimetry on BESHI / T. Hu (contribution not received) -- The crystal ball and TAPS detectors at the MAMI electron beam facility / D. Watts -- Front-end electronics of the ATLAS tile calorimeter / R. Teuscher -- The ATLAS tilecal detector control system / A. Gomes -- Performance of the liquid argon final calibration board / C. de la Taille -- Overview of the LHCb calorimeter electronics / F. Machefert -- LHCb preshower photodetector and electronics / S. Monteil -- The CMS ECAL readout architecture and the clock and control system / K. Kloukinas -- Test of the CMS-ECAL trigger primitive generation / N. Regnault -- Optical data links for the CMS ECAL / J. Grahl (contribution not received) -- CMS ECAL off-detector electronics / R. Alemany Fernandez -- Performance of a low noise readout ASIC for the W-Si calorimeter physics prototype for the future linear collider / C. de la Taille -- Properties of a sampling calorimeter with warm-liquid ionization chambers / S. Plewnia -- Calorimetry and the DO experiment / R. Zitoun (contribution not received) -- Data quality monitoring for the DØ calorimeter / V. Shary -- Status of the construction of the ATLAS electromagnetic liquid argon calorimeter, overview of beam test performance studies / L. Serin -- Uniformity of response of ATLAS liquid argon EM calorimeter / O. Gaunter -- Status of the ATLAS liquid argon hadronic endcap calorimeter construction / M. Vincter -- Results from particle beam tests of the ATLAS liquid argon endcap calorimeters / M. Lefebvre -- First results of the DREAM project / R. Wigmans -- Electron and muon detection with a dual-readout (DREAM) calorimeter / N. Akchurin -- The neutron zero degree calorimeter for the ALICE experiment / M. Gallio -- The liquid xenon scintillation calorimeter of the MEG experiment: operation of a large prototype / G. Signorelli -- Detection of high energy particles using radio frequency signals / C. Hebert -- Hadronic shower simulation / J.-P. Wellisch -- E.M. and hadronic shower simulation with FLUKA / G. Battistoni -- Simulation of the LHCb electromagnetic calorimeter response with GEANT4 / P. Robbe -- Comparison of beam test results of the combined ATLAS liquid argon endcap calorimeters with GEANT3 and GEANT4 simulations / D. Salihagić -- GEANT4 hadronic physics validation with LHC test-beam data / C. Alexa -- The full simulation of the GLAST LAT high energy gamma ray telescope / F. Longo -- Response of the KLOE electromagnetic calorimeter to low-energy particles / T. Spadaro -- Calorimeter algorithms for DØ; / S. Trincaz-Duvoid -- Identification of low P[symbol] muon with the ATLAS tile calorimeter / G. Usai -- Electron and photon reconstruction with fully simulated events in the CMS experiment / G. Daskalakis -- Expected performance of Jet, [symbol] and [symbol] reconstruction in ATLAS / I. Vivarelli -- LHCb calorimeter from trigger to physics / O. Deschamps -- The calibration strategy of CMS electromagnetic calorimeter / P. Meridiani -- Energy and impact point reconstruction in the CMS ECAL (testbeam results from 2003) / I. B. van Vulpen -- The jet energy scale and resolution in the DO calorimeter / A. Kupco (contribution not received) -- Precision linearity studies of the ATLAS liquid argon EM calorimeter / G. Graziani -- Calibration of the ATLAS tile calorimeter / F. Sarri -- Performance of the CMS ECAL laser monitoring source in the test beam / A. Bornheim -- Energy reconstruction algorithms and their influence on the ATLAS tile calorimeter / E. Fullana -- Study of the biological effectiveness of ionizing radiations for a more realistic evaluation of the radiation quality in hadrontherapy / R. Cherubini (contribution not received) -- New dosimetry technologies for IMRT (Intensity Modulated Radio Therapy) / A. Piermattei -- Photon neutron radiotherapy / G. Giannini (contribution not received) -- Recent developments in molecular imaging / G. Zavattini (contribution not received) -- Performance goals and design considerations for a linear collider calorimeter / F. Sefkow -- Improving the jet reconstruction with the particle flow method; an introduction / J.-C. Brient -- Fine grained SiW ECAL for a linear collider detector / D. Strom (in the silicon session) -- Silicon-tungsten sampling electromagnetic calorimeter for the TeV electron-positron linear collider / J.-C. Brient -- LCCAL: a calorimeter prototype for future linear colliders / S. Miscetti -- Analog vs digital hadron calorimetry at a future electron-positron linear collider / S. Magill -- Toward a scintillator based heal and tail catcher for the LC calorimeter / M. Martin (contribution not received) -- Minical options, description in MC, calibration, plans for test beam prototype / G. Eigen (contribution not received) -- Photodetector options for a scintillator heal / E. Popova (contribution not received) -- Very low background scintillators in DAMA project: results and perspectives / R. Bernabei -- EDELWEISS Ge cryogenics detectors: main performance and physics results / X. Navick (contribution not received) -- Review of massive underground detectors / A. Rubbia -- Review of neutrino telescopes underwater and under ice / A. Capone (contribution not received) -- The fluorescence detector of the Pierre Auger Observatory / R. Caruso -- The EUSO mission for the observation of ultra high energy cosmic rays from space / A. Petrolini -- Performance of a 3D imaging electromagnetic calorimeter for the AMSO2 space experiment / C. Adloff -- Beam test calibration of the balloon borne imaging calorimeter for the CREAM experiment / P. Maestro.

Novel antidepressant candidate RO-05 modulated glucocorticoid receptors activation and FKBP5 expression in chronic mild stress model in rats.

PubMed

Xing, Y; Hou, J; Meng, Q; Yang, M; Kurihara, H; Tian, J

2015-04-02

In this study, a novel TRI (triple reuptake inhibitors) antidepressant candidate RO-05 (4-[1-[1-(benzoyloxy)cyclohexyl]-2-(dimethylamino)ethyl]-phenyl benzoate) was investigated in TST (tail suspension test), FST (forced swimming test) and CMS (chronic mild stress) model. Results showed RO-05 significantly decreased the immobility time in FST and TST at 4.5-, 9-, 18-mg/kg in rats and 9-, 18-, 36-mg/kg in mice. Chronic administration of 18-mg/kg RO-05 improved the behavioral index, anhedonia and normalized the hyperactivity of HPA (hypothalamic-pituitary-adrenal axis) of CMS rats. We further investigated the possible mechanisms of RO-05 in the CMS model. Eighteen milligrams per kilogram of RO-05 chronic administration significantly reversed the increase of mRNA and protein expression of FKBP5 in the CMS rat hippocampus, which facilitated the activation of GR- (glucocorticoid receptor) and GR-responsive gene Foxo1 expression. RO-05 also elevated the expression of BDNF (brain-derived neurotrophic factor) in CMS rat hippocampus. In summary, our results indicated that RO-05 is a promising antidepressant candidate. The possible antidepressant mechanisms of RO-05 were the modulation of FKBP5 expression, GR activation, corresponding inhibition of HPA axis hyperactivity, and the increase of BDNF expression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

NASA's Carbon Monitoring System (CMS) Applications and Application Readiness Levels (ARLs)-An assessment of how all CMS ARLs provide societal benefit.

NASA Astrophysics Data System (ADS)

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

2016-12-01

During the past six years, the NASA Carbon Monitoring System (CMS) Applications effort has been engaging with stakeholders in an effort to make the 52 CMS project user friendly and policy relevant. Congressionally directed, the CMS initiative is a NASA endeavor providing carbon data products that help characterize and understand carbon sources and sinks at local and international scales. All data are freely available, and scaled for local, state, regional, national and international-level resource management. To facilitate user feedback during development, as well as understanding for the type of use and application the CMS data products can provide, the Applications project utilizes the NASA Applied Sciences Program nine step Application Readiness Level (ARL) indices. These are used to track and manage the progression and distribution of funded projects. ARLs are an adaptation of NASA's technology readiness levels (TRLs) used for managing technology and risk and reflects the three main tiers of a project: research, development and deployment. The ARLs are scaled from 1 to 9, research and development (ARL1) to operational and/or decision making ready products (ARL9). The ARLS can be broken up into three phases: Phase 1, discovery and feasibility (ARL 1-3); Phase 2, development testing and validation (ARL 4-6); and Phase 3, integration into Partner's systems (ARL 7-9). The ARLs are designed to inform both scientist and end user of the product maturity and application capability. The CMS initiative has products that range across all ARLs, providing societal benefit at multiple scales. Lower ARLs contribute to formal documents such as the IPCC while others at higher levels provide decision support quantifying the value of carbon data for greenhouse gas (GHG) reduction planning. Most CMS products have an ARL 5, (validation of a product in a relevant environment), meaning the CMS carbon science is actively in a state of science-user engagement. For the user community, ARLs are a litmus test for knowing the type of user feedback and advocacy that can be implemented into the product design. For the scientist, ARLS help communicate (1) the maturity of their science to users who would like to use it for decision making and (2) the intended use of the product.

Ada Compiler Validation Summary Report: Certificate Number 89020W1. 10073: International Business Machines Corporation, IBM Development System for the Ada Language, VM/CMS Ada Compiler, Version 2.1.1, IBM 3083 (Host and Target)

DTIC Science & Technology

1989-04-20

International Business Machines Corporation) IBM Development System for the Ada Language, VN11/CMS Ada Compiler, Version 2.1.1, Wright-Patterson AFB, IBM 3083...890420W1.10073 International Business Machines Corporation IBM Development System for the Ada Language VM/CMS Ada Compiler Version 2.1.1 IBM 3083... International Business Machines Corporation and reviewed by the validation team. The compiler was tested using all default option settings except for the

Ada Compiler Validation Summary Report: Certificate Number: 890420W1. 10075 International Business Machines Corporation. IBM Development System, for the Ada Language CMS/MVS Ada Cross Compiler, Version 2.1.1 IBM 3083 Host and IBM 4381 Target

DTIC Science & Technology

1989-04-20

International business Machines Corporati,:i IBM Development System for the Ada Language, CMS/MVS Ada Cross Compiler, Version 2.1.1, Wright-Patterson AFB, IBM...VALIDATION SUMMARY REPORT: Certificate Number: 890420W1.10075 International Business Machines Corporation IBM Development System for the Ada Language CMS...command scripts provided by International Business Machines Corporation and reviewed by the validation team. The compiler was tested using all default

Effect of strawberry (Fragaria x ananasa) as antidepresant activity on mice induced by stress

NASA Astrophysics Data System (ADS)

Hazar, Siti; Fitri, Lulu L.

2015-09-01

Depression is a physiological disorder on the brain and may induce the reduction levels of monoamine neurotransmitters, serotonin and the increased levels of stress hormone, corticosterone. The use of antidepressant drugs causing side effect, therefore natural agents are used as alternative therapy. The objectives of this study are to determine the effect of strawberries in the murine experiments in increasing serotonin level as well as decreasing in the immobility time of mice on Forced Swimming Task (FST). Forty-eight male outbreed of 4 weeks old mice strain Swiss Webster with average body weight of 18-22 grams were divided into six groups of eight mice, as follows: (1) non-stressed, (2) Chronic Mild Stressed (CMS), (3) strawberry extract (with dose of 464.1 mg/kg) and CMS, (4) strawberry extract (with dose of 928.2 mg/kg) and CMS, (5) fisetin (with a dose of 10 mg/kg) and CMS, and (6) amitriptyline (an antidepressant, with a dose of 3.25 mg/kg) and CMS as a comparison group. Chronic Mild Stress (CMS) method were used as induction of stress consisted of seven different stressors and assigned randomly for 35 days. Provision of treatment was made during the 14 days preparations on day 22 to day 35. At the end of treatments, all mice were assigned on FST test for immobility time measurements. Next, all mice were decapitated and the brains were isolated. Serotonin levels were measured using High Performance Liquid Chromatography (HPLC) with UV-visible light detector. The results showed that the immobility time of group mice which were given by the strawberries (928.2 mg/kg) and fisetin had shorter duration than the positive control group. Furthermore, the level of serotonin in the test group increased compared to CMS group. Corticosterone levels of treatment mice were increased significantly compared to non-stressed mice. Therefore, it can be concluded that strawberries are able to improve depressive symptoms by decreasing immobility time and increasing levels of serotonin compared with CMS group.

Large Scale Beam-Tests of the Silicon and Scintillator-SiPM Modules for the CMS High Granularity Calorimeter at the HL-LHC

NASA Astrophysics Data System (ADS)

Jain, Shilpi

The High Granularity Calorimeter (HGCAL) will replace the existing CMS endcap calorimeters during the High Luminosity run of the LHC (HL-LHC) era. The electromagnetic part, as well as the first layers of the hadronic part, foresees around 600 square metres of silicon sensors as the active material. The remainder of the HGCAL, in the lower radiation environment, will use plastic scintillators with on-tile silicon photomultiplier (SiPM) readout. Prototype hexagonal silicon modules, featuring a new ASIC (Skiroc2-CMS), together with a modified version of the scintillator-SiPM CALICE AHCAL, have been tested in beams at CERN. This setup represents a full slice through HGCAL. Results from MIP calibration, energy resolution, electromagnetic and hadronic shower-shapes are presented using electrons, pions and muons.

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.

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

PubMed

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

2015-05-01

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

[Genetics of fertility restoration in the isocytoplasm allonuclear C-group of cytoplasmic male sterility in maize].

PubMed

Zhao, Zhuo Fan; Huang, Ling; Liu, Yong Ming; Zhang, Peng; Wei, Gui; Cao, Mo Ju

2018-05-20

Maize is one of the first crops to produce hybrids using cytoplasmic male sterile lines. The C-type cytoplasmic male sterile (CMS-C) line is vital for hybrid seed production, and the fertility-restoration reaction along with its stability has a direct bearing on its applications. However, fertility restoration mechanism of CMS-C is complex and is still not clear so far. To further explore the factors affecting the fertility restoration of maize CMS, a series of test crosses were carried out by pollinating the isocytoplasm allonuclear CMS-C lines C48-2, Chuangzaosi and C478 with the test lines 18 bai, zi 330, 5022 and the restorer line A619, respectively. Four F 2 populations and six double-cross combinations were obtained from the self-cross of fertility restored F 1 and pollinating male-sterility-maintained F 1 with the male-fertility-restored F 1 , respectively. Meanwhile, we developed the incomplete diallel-cross combinations using the isocytoplasm allonuclear male sterile lines as maternal parents and their respective maintainer lines 48-2, huangzaosi and 478 as paternal parents. All the F 1 , F 2 and double-cross populations were planted at distinct locations in different years, and the fertility-restoration reaction was scored by field investigation and pollen staining with I 2 -IK. The results were as follows: 1) The same test line could restore the CMS-C line at a certain genetic background, but failed to restore the CMS-C line at the other genetic backgrounds, suggesting that the genetic background of CMS-C lines plays an important role in the fertility restoration. 2) The fertile-to-sterile segregation ratio of (C48-2×A619) F 2 population planted in both Sichuan and Yunnan fited well to 15:1 by the χ 2 test. However, the fertility level of individuals in Yunnan mainly belonged to the 3 and 4grades, but which in Sichuan mainly belonged to the 5 grade, indicating the environmental factors had effect on the fertility-restoration reaction of (C48-2×A619) F 2 . 3) In our study, 18 bai could not restore C478, and 48-2 could not restore C478, but the fertile and sterile segregated plants were unexpectedly found in their double-cross population [(C478×18 bai) F 1S ×(C48-2×18 bai) F 1F ]. The similar case was also observed in the double-cross population [(C48-2 × zi 330) F 1S × (C478 × zi 330) F 1F ]. Therefore, we speculated that there are minor fertility restorer genes not only in the nuclear background of C48-2 and C478, but also in zi 330 and 18 bai, and when these minor genes were gathered by hybridization, they could restore the fertility of C478 and C48-2. This conforms to the restorer genes dose-effect for fertility restoration in the plant CMS system. These results not only contribute to our understanding of the complexity and diversity of CMS-C restoration mechanism, but also provide an important reference for the practical applications about maize CMS-C.

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

PubMed

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

2018-01-01

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

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.

Using tevatron magnets for HE-LHC or new ring in LHC tunnel

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

Piekarz, Henryk; /Fermilab

Two injector accelerator options for HE-LHC of p{sup +} - p{sup +} collisions at 33 TeV cms energy are briefly outlined. One option is based on the Super-SPS (S-SPS) accelerator in the SPS tunnel, and the other one is based on the LER (Low-Energy-Ring) accelerator in the LHC tunnel. Expectations of performance of the main arc accelerator magnets considered for the construction of the S-SPS and of the LER accelerators are used to tentatively devise some selected properties of these accelerators as potential injectors to HE-LHC.

Comparison of myocardial ischemia during intense mental stress using flight simulation in airline pilots with coronary artery disease to that produced with conventional mental and treadmill exercise stress testing.

PubMed

Doorey, Andrew; Denenberg, Barry; Sagar, Vidya; Hanna, Tracy; Newman, Jack; Stone, Peter H

2011-09-01

Mental stress increases cardiovascular morbidity and mortality. Although laboratory mental stress often causes less myocardial ischemia than exercise stress (ES), it is unclear whether mental stress is intrinsically different or differences are due to less hemodynamic stress with mental stress. We sought to evaluate the hemodynamic and ischemic response to intense realistic mental stress created by modern flight simulators and compare this response to that of exercise treadmill testing and conventional laboratory mental stress (CMS) testing in pilots with coronary disease. Sixteen airline pilots with angiographically documented coronary disease and documented myocardial ischemia during ES were studied using maximal treadmill ES, CMS, and aviation mental stress (AMS) testing. AMS testing was done in a sophisticated simulator using multiple system failures as stressors. Treadmill ES testing resulted in the highest heart rate, but AMS caused a higher blood pressure response than CMS. Maximal rate-pressure product was not significantly different between ES and AMS (25,646 vs 23,347, p = 0.08), although these were higher than CMS (16,336, p <0.0001). Despite similar hemodynamic stress induced by ES and AMS, AMS resulted in significantly less ST-segment depression and nuclear ischemia than ES. Differences in induction of ischemia by mental stress compared to ES do not appear to be due to the creation of less hemodynamic stress. In conclusion, even with equivalent hemodynamic stress, intense realistic mental stress induced by flight simulators results in significantly less myocardial ischemia than ES as measured by ST-segment depression and nuclear ischemia. Copyright © 2011 Elsevier Inc. All rights reserved.

First Experiences with CMS Data Storage on the GEMSS System at the INFN-CNAF Tier-1

NASA Astrophysics Data System (ADS)

Andreotti, D.; Bonacorsi, D.; Cavalli, A.; Pra, S. Dal; Dell'Agnello, L.; Forti, Alberto; Grandi, C.; Gregori, D.; Gioi, L. Li; Martelli, B.; Prosperini, A.; Ricci, P. P.; Ronchieri, Elisabetta; Sapunenko, V.; Sartirana, A.; Vagnoni, V.; Zappi, Riccardo

A brand new Mass Storage System solution called "Grid-Enabled Mass Storage System" (GEMSS) -based on the Storage Resource Manager (StoRM) developed by INFN, on the General Parallel File System by IBM and on the Tivoli Storage Manager by IBM -has been tested and deployed at the INFNCNAF Tier-1 Computing Centre in Italy. After a successful stress test phase, the solution is now being used in production for the data custodiality of the CMS experiment at CNAF. All data previously recorded on the CASTOR system have been transferred to GEMSS. As final validation of the GEMSS system, some of the computing tests done in the context of the WLCG "Scale Test for the Experiment Program" (STEP'09) challenge were repeated in September-October 2009 and compared with the results previously obtained with CASTOR in June 2009. In this paper, the GEMSS system basics, the stress test activity and the deployment phase -as well as the reliability and performance of the system -are overviewed. The experiences in the use of GEMSS at CNAF in preparing for the first months of data taking of the CMS experiment at the Large Hadron Collider are also presented.

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

NASA Astrophysics Data System (ADS)

Quast, Thorben

2018-02-01

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

Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications.

PubMed

Di Baldassarre, Angela; Cimetta, Elisa; Bollini, Sveva; Gaggi, Giulia; Ghinassi, Barbara

2018-05-25

Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

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

NASA Astrophysics Data System (ADS)

Fedi, Giacomo

2017-08-01

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

The development and validation of the Closed-set Mandarin Sentence (CMS) test.

PubMed

Tao, Duo-Duo; Fu, Qian-Jie; Galvin, John J; Yu, Ya-Feng

2017-09-01

Matrix-styled sentence tests offer a closed-set paradigm that may be useful when evaluating speech intelligibility. Ideally, sentence test materials should reflect the distribution of phonemes within the target language. We developed and validated the Closed-set Mandarin Sentence (CMS) test to assess Mandarin speech intelligibility in noise. CMS test materials were selected to be familiar words and to represent the natural distribution of vowels, consonants, and lexical tones found in Mandarin Chinese. Ten key words in each of five categories (Name, Verb, Number, Color, and Fruit) were produced by a native Mandarin talker, resulting in a total of 50 words that could be combined to produce 100,000 unique sentences. Normative data were collected in 10 normal-hearing, adult Mandarin-speaking Chinese listeners using a closed-set test paradigm. Two test runs were conducted for each subject, and 20 sentences per run were randomly generated while ensuring that each word was presented only twice in each run. First, the level of the words in each category were adjusted to produce equal intelligibility in noise. Test-retest reliability for word-in-sentence recognition was excellent according to Cronbach's alpha (0.952). After the category level adjustments, speech reception thresholds (SRTs) for sentences in noise, defined as the signal-to-noise ratio (SNR) that produced 50% correct whole sentence recognition, were adaptively measured by adjusting the SNR according to the correctness of response. The mean SRT was -7.9 (SE=0.41) and -8.1 (SE=0.34) dB for runs 1 and 2, respectively. The mean standard deviation across runs was 0.93 dB, and paired t-tests showed no significant difference between runs 1 and 2 (p=0.74) despite random sentences being generated for each run and each subject. The results suggest that the CMS provides large stimulus set with which to repeatedly and reliably measure Mandarin-speaking listeners' speech understanding in noise using a closed-set paradigm.

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

PubMed

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

2015-06-01

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

Decoupling suspension controller based on magnetic flux feedback.

PubMed

Zhang, Wenqing; Li, Jie; Zhang, Kun; Cui, Peng

2013-01-01

The suspension module control system model has been established based on MIMO (multiple input and multiple output) state feedback linearization. We have completed decoupling between double suspension points, and the new decoupling method has been applied to CMS04 magnetic suspension vehicle in national mid-low-speed maglev experiment field of Tangshan city in China. Double suspension system model is very accurate for investigating stability property of maglev control system. When magnetic flux signal is taken back to the suspension control system, the suspension module's antijamming capacity for resisting suspension load variety has been proved. Also, the external force interference has been enhanced. As a result, the robustness and stability properties of double-electromagnet suspension control system have been enhanced.

Decoupling Suspension Controller Based on Magnetic Flux Feedback

PubMed Central

Zhang, Wenqing; Li, Jie; Zhang, Kun; Cui, Peng

2013-01-01

The suspension module control system model has been established based on MIMO (multiple input and multiple output) state feedback linearization. We have completed decoupling between double suspension points, and the new decoupling method has been applied to CMS04 magnetic suspension vehicle in national mid-low-speed maglev experiment field of Tangshan city in China. Double suspension system model is very accurate for investigating stability property of maglev control system. When magnetic flux signal is taken back to the suspension control system, the suspension module's antijamming capacity for resisting suspension load variety has been proved. Also, the external force interference has been enhanced. As a result, the robustness and stability properties of double-electromagnet suspension control system have been enhanced. PMID:23844415

A compact permanent magnet cyclotrino for accelerator mass spectrometry

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

Young, A.T.; Clark, D.J.; Kunkel, W.B.

1995-02-01

The authors describe the development of a new instrument for the detection of trace amounts of rare isotopes, a Cyclotron Mass Spectrometer (CMS). A compact low energy cyclotron optimized for high mass resolution has been designed and has been fabricated. The instrument has high sensitivity and is designed to measure carbon-14 at abundances of < 10{sup {minus}12}. A novel feature of the instrument is the use of permanent magnets to energize the iron poles of the cyclotron. The instrument uses axial injection, employing a spiral inflector. The instrument has been assembled and preliminary measurements of the magnetic field show thatmore » it has a uniformity on the order of 2 parts in 10{sup 4}.« less

A Systematic Review of Intervention Studies Examining Nutritional and Herbal Therapies for Mild Cognitive Impairment and Dementia Using Neuroimaging Methods: Study Characteristics and Intervention Efficacy

PubMed Central

MacMillan, Freya; Camfield, David A.; Seto, Sai W.

2017-01-01

Neuroimaging facilitates the assessment of complementary medicines (CMs) by providing a noninvasive insight into their mechanisms of action in the human brain. This is important for identifying the potential treatment options for target disease cohorts with complex pathophysiologies. The aim of this systematic review was to evaluate study characteristics, intervention efficacy, and the structural and functional neuroimaging methods used in research assessing nutritional and herbal medicines for mild cognitive impairment (MCI) and dementia. Six databases were searched for articles reporting on CMs, dementia, and neuroimaging methods. Data were extracted from 21/2,742 eligible full text articles and risk of bias was assessed. Nine studies examined people with Alzheimer's disease, 7 MCI, 4 vascular dementia, and 1 all-cause dementia. Ten studies tested herbal medicines, 8 vitamins and supplements, and 3 nootropics. Ten studies used electroencephalography (EEG), 5 structural magnetic resonance imaging (MRI), 2 functional MRI (fMRI), 3 cerebral blood flow (CBF), 1 single photon emission tomography (SPECT), and 1 positron emission tomography (PET). Four studies had a low risk of bias, with the majority consistently demonstrating inadequate reporting on randomisation, allocation concealment, blinding, and power calculations. A narrative synthesis approach was assumed due to heterogeneity in study methods, interventions, target cohorts, and quality. Eleven key recommendations are suggested to advance future work in this area. PMID:28303161

Cavernous malformations isolated from cranial nerves: Unexpected diagnosis?

PubMed

Rotondo, Michele; Natale, Massimo; D'Avanzo, Raffaele; Pascale, Michela; Scuotto, Assunta

2014-11-01

Cranial nerves (CN) cavernous malformations (CMs) are lesions that are isolated from the CNs. The authors present three cases of CN CMs, for which MR was demonstrated to be critical for management, and surgical resection produced good outcomes for the patients. Surgical removal is the recommended course of action to restore or preserve neurological function and to eliminate the risk of future haemorrhage. However, the anatomical location and the complexity of nearby neural structures can make these lesions difficult to access and remove. In this study, the authors review the literature of reported cases of CN CMs to analyse the clinical and radiographic presentations, surgical approaches and neurological outcomes. A MEDLINE/Pub Med search was performed and revealed 86 cases of CN CMs. The authors report three additional cases in this study for a total of 89 cases. CMs affecting the optic nerve (CN II), oculomotor nerve (CN III), facial/vestibule-cochlear nerves (CN VII, CN VIII) have been described. The records of three patients were reviewed with respect to the lesion locations, symptoms, surgical approaches and therapeutic considerations. Clinical and radiological follow-up results are reported. Three patients (2 females, 1 male; age range 21-37 year) presented with three CN lesions. One lesion involved CN III, one lesion involved CN VII-CN VIII, and one involved CN II. The patient with the CN III lesion had a one-month history of mild right ptosis and diplopia. The patient with the CN VII-CN VIII lesion exhibited acute hearing loss and on the left and left facial paresis. The patient with the opticchiasmatic lesion presented with acute visual deterioration on the right and a left temporal field deficit in the left eye. Pterional and orbitozygomatic craniotomies were performed for the CN III lesion and the CN II lesion, and retrosigmoid craniotomy was performed for the cerebello-pontine angle lesion. All patients experienced symptom improvement after surgery. On MR follow-up, recurrence was excluded in all patients. CN CMs present with specific symptoms and require complex surgical techniques for resection. These lesions are frequently symptomatic, because of the complexity of the origin tissue. Symptomatic CN CMs should be resected microsurgically and completely when possible to prevent further losses of nerve function, improve function, avoid recurrence, and to eliminate the risk of future haemorrhages. The authors discuss the therapeutic options and the radiological features of these infrequent localisation of CMs. Specifically, the authors focus on the role of magnetic resonance imaging in the identification of these rare lesions. Copyright © 2014 Elsevier B.V. All rights reserved.

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].

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.

Functional expression and pharmaceutical efficacy of cardiac-specific ion channels in human embryonic stem cell-derived cardiomyocytes.

PubMed

Kim, Han Sol; Yoon, Jung Won; Li, Hongliang; Jeong, Geun Ok; Park, Jin Ju; Shin, Sung Eun; Jang, Il Ho; Kim, Jae Ho; Park, Won Sun

2017-10-23

Cardiomyocytes differentiated from human pluripotent stem cells provide promising tools for screening of cardiotoxic drugs. For evaluation of human pluripotent stem cell-derived cardiomyocytes for cardiotoxicity test, in the present study, human embryonic stem cells (hESCs) were differentiated to cardiomyocytes, followed by metabolic selection to enrich the differentiated cardiomyocytes. The highly purified hESC-derived cardiomyocytes (hESC-CMs) expressed several cardiomyocyte-specific markers including cTnT, MLC2a, and α-SA, but not pluripotency markers, such as OCT4 and NANOG. Patch clamp technique and RT-PCR revealed the expression of cardiomyocyte-specific Na + , Ca 2+ , and K + channels and cardiac action potential in hESC-CMs. To explore the potential use of hESC-CMs as functional cardiomyocytes for drug discovery and cardiotoxicity screening, we examined the effects of bisindolylmaleimide (BIM) (I), which inhibits native cardiac Ca 2+ channels, on the Ca 2+ channel activity of hESC-CMs. We observed a similar response for the BIM (I)-induced modulation of Ca 2+ channels between hESC-CMs and native cardiomyocytes through L-type Ca 2+ channel current. These results suggest that hESC-CMs can be useful for evaluation of pharmaceutical efficacy and safety of novel drug candidate in cardiac research.

Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.

PubMed

Gong, Xue-Lian; Gao, Ting-Ting; Zhao, Li-Jun; Zhu, Hai; Xia, Zhen-Na; Lu, Wen; Lu, Guo-Cai

2014-08-01

CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions. Copyright © 2014 Elsevier Inc. All rights reserved.

Gender Differences in Physical Performance Characteristics of Elite Surfers.

PubMed

Parsonage, Joanna R; Secomb, Josh L; Tran, Tai T; Farley, Oliver R L; Nimphius, Sophia; Lundgren, Lina; Sheppard, Jeremy M

2017-09-01

Parsonage, JR, Secomb, JL, Tran, TT, Farley, ORL, Nimphius, S, Lundgren, L, and Sheppard, JM. Gender differences in physical performance characteristics of elite surfers. J Strength Cond Res 31(9): 2417-2422, 2017-The purpose of this study was to describe and compare the gender differences in physical performance characteristics of elite surfers. Twenty competitive female surfers (CFS) and 20 competitive male surfers (CMS) performed a battery of physical performance tests: squat jump (SJ), isometric midthigh pull (IMTP), 15-m sprint paddle, and 400-m endurance paddle during a single testing session. All performance measures were significantly different between CFS and CMS (p < 0.01). Specifically, CMS produced greater peak force production (28.5%) and jumped higher (27.7%) in the SJ and produced greater normalized peak force during the IMTP (18.9%) compared with CFS. For paddling performance, CMS were faster over 5, 10, and 15 m (12.4%, 9.7%, and 10.9%), possessed a higher peak paddling velocity (11.3%), and recorded faster paddle times over 400 m (11.8%). The results of this study suggest that CMS exhibit superior physical performance characteristics than CFS, in relation to both the lower and upper body. Strength and conditioning practitioners should therefore implement a structured and periodized program to facilitate strength qualities that underpin surfing performance for all participants, but as highlighted in the current investigation, female surfers may have a greater window for adaptation and therefore vast benefit of targeting their underdeveloped physical qualities.

The long journey to the Higgs boson and beyond at the LHC: Emphasis on ATLAS

NASA Astrophysics Data System (ADS)

Jenni, Peter

2016-09-01

The journey in search for the Higgs boson with the ATLAS and CMS experiments at the Large Hadron Collider (LHC) at CERN started more than two decades ago. But the first discussions motivating the LHC project dream date back even further into the 1980s. This article will recall some of these early historical considerations, mention some of the LHC machine milestones and achievements, focus as an example of a technological challenge on the unique ATLAS superconducting magnet system, and then give an account of the physics results so far, leading to, and featuring particularly, the Higgs boson results, and sketching finally prospects for the future. With its emphasis on the ATLAS experiment it is complementary to the preceding article by Tejinder S. Virdee which focused on the CMS experiment.

The Long Journey to the Higgs Boson and Beyond at the LHC Part II: Emphasis on ATLAS

NASA Astrophysics Data System (ADS)

Jenni, Peter

The journey in search for the Higgs boson with the ATLAS and CMS experiments at the Large Hadron Collider (LHC) at CERN started more than two decades ago. But the first discussions motivating the LHC project dream date back even further into the 1980s. This article will recall some of these early historical considerations, mention some of the LHC machine milestones and achievements, focus as an example of a technological challenge on the unique ATLAS superconducting magnet system, and then give an account of the physics results so far, leading to, and featuring particularly, the Higgs boson results, and sketching finally prospects for the future. With its emphasis on the ATLAS experiment it is complementary to the preceding article by Tejinder S. Virdee which focused on the CMS experiment.

Association Between Medicare Summary Star Ratings for Patient Experience and Clinical Outcomes in US Hospitals.

PubMed

Trzeciak, Stephen; Gaughan, John P; Bosire, Joshua; Mazzarelli, Anthony J

2016-03-01

In 2015, the Centers for Medicare and Medicaid Services (CMS) released new summary star ratings for US hospitals based on patient experience. We aimed to test the association between CMS patient experience star ratings and clinical outcomes. We analyzed risk-adjusted data for more than 3000 US hospitals from CMS Hospital Compare using linear regression. We found that better patient experience was associated with favorable clinical outcomes. Specifically, a higher number of stars for patient experience had a statistically significant association with lower rates of many in-hospital complications. A higher patient experience star rating also had a statistically significant association with lower rates of unplanned readmissions to the hospital within 30 days. Better patient experience according to the CMS star ratings is associated with favorable clinical outcomes. These results support the inclusion of patient experience data in the framework of how hospitals are paid for services.

Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation.

PubMed

Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P

2017-02-01

Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These two cell types demonstrate similar effects in promoting the compaction and cell spreading, as well as expression of maturation markers at both gene and protein levels. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of twitch force, elastic modulus, sarcomere length and molecular signature, when comparing to static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture. Our results therefore suggest that this 3D model can be used for in vitro cardiac maturation study. Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as being a promising source of cells for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. In the current study, we have fabricated cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials and demonstrated that supplementation of mesenchymal niche cells as well as provision of mechanical loading particularly stretching have significantly promoted the maturation of the cardiomyocytes and hence improved the mechanical functional characteristics of the tissue strips. Specifically, with 3% niche cells including both fibroblasts and mesenchymal stem cells, a more mature hESC-CMs derived cardiac strip was resulted, in terms of compaction and spreading of cells, and upregulation of molecular signature in both gene and protein expression of maturation. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of molecular signature markers and functional parameters including twitch force, elastic modulus and sarcomere length, when comparing with static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture, resulting in more mature cardiac strips. Our results contribute to bioengineering of functional heart tissue strips for drug screening and disease modeling. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-08-29

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

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

PubMed

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

2013-07-01

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

Magnet® Hospital Recognition Linked to Lower Central Line-Associated Bloodstream Infection Rates

PubMed Central

Barnes, Hilary; Rearden, Jessica; McHugh, Matthew D.

2016-01-01

Central-line-associated bloodstream infections (CLABSI) are among the deadliest heathcare-associated infections, with an estimated 12–25% mortality rate. In 2014, the Centers for Medicare and Medicaid Services (CMS) began to penalize hospitals for poor performance with respect to selected hospital-acquired conditions, including CLABSI. A structural factor associated with high-quality nursing care and better patient outcomes is The Magnet Recognition Program®. The purpose of this study was to explore the relationship between Magnet status and hospital CLABSI rates. We used propensity score matching to match Magnet and non-Magnet hospitals with similar hospital characteristics. In a matched sample of 291 Magnet hospitals and 291 non-Magnet hospitals, logistic regression models were used to examine whether there was a link between Magnet status and CLABSI rates. Both before and after matching, Magnet hospital status was associated with better (lower than the national average) CLABSI rates (OR = 1.60, 95% CI: 1.10, 2.33 after matching). While established programs such as Magnet recognition are consistently correlated with high-quality nursing work environments and positive patient outcomes, additional research is needed to determine whether Magnet designation produces positive patient outcomes or rewards existing excellence. PMID:26809115

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

Hasegawa, S.

The CMS pixel phase-1 upgrade project replaces the current pixel detector with an upgraded system with faster readout electronics during the extended year-end technical stop of 2016/2017. New electronics prototypes for the system have been developed, and tests in a realistic environment for a comprehensive evaluation are needed. A full readout test stand with either the same hardware as used in the current CMS pixel detector or the latest prototypes of upgrade electronics has been built. The setup enables the observation and investigation of a jitter increase in the data line associated with trigger rate increases. This effect is duemore » to the way in which the clock and trigger distribution is implemented in CMS. A new prototype of the electronics with a PLL based on a voltage controlled quartz crystal oscillator (QPLL), which works as jitter filter, in the clock distribution path was produced. With the test stand, it was confirmed that the jitter increase is not seen with the prototype, and also good performance was confirmed at the expected detector operation temperature ($-$20 °C).« less

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

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

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

2016-04-01

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

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.

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.

Isolation stress and chronic mild stress induced immobility in the defensive burying behavior and a transient increased ethanol intake in Wistar rats.

PubMed

Vázquez-León, Priscila; Martínez-Mota, Lucía; Quevedo-Corona, Lucía; Miranda-Páez, Abraham

2017-09-01

Stress can be experienced with or without adverse effects, of which anxiety and depression are two of the most important due to the frequent comorbidity with alcohol abuse in humans. Historically, stress has been considered a cause of drug use, particularly alcohol abuse due to its anxiolytic effects. In the present work we exposed male Wistar rats to two different stress conditions: single housing (social isolation, SI), and chronic mild stress (CMS). We compared both stressed groups to group-housed rats and rats without CMS (GH) to allow the determination of a clear behavioral response profile related to their respective endocrine stress response and alcohol intake pattern. We found that SI and CMS, to a greater extent, induced short-lasting increased sucrose consumption, a transient increase in serum corticosterone level, high latency/immobility, and low burying behavior in the defensive burying behavior (DBB) test, and a transient increase in alcohol intake. Thus, the main conclusion was that stress caused by both SI and CMS induced immobility in the DBB test and, subsequently, induced a transient increased voluntary ethanol intake in Wistar rats with a free-choice home-cage drinking paradigm. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-15

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

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

PubMed Central

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

2013-01-01

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

Commissioning of the first chambers of the CMS GE1/1 muon station

NASA Astrophysics Data System (ADS)

Ressegotti, Martina; CMS Muon Group

2017-12-01

The upgrades of the LHC planned in the next years will increase the instantaneous luminosity up to 5 × 1034 cm -2 s -1 after Long Shutdown 3, a value about five times higher than the nominal one for which the CMS experiment was designed. The resulting larger rate of interactions will produce a higher pileup environment that will challenge the trigger system of the CMS experiment in its original configuration, in particular in the endcap region. As part of the upgrade program of the CMS muon endcaps, additional muon detectors based on Gas Electron Multiplier (GEM) technology will be installed, in order to be able to sustain a physics program during high-luminosity operation without performance losses. The installation of the GE1/1 station is scheduled for Long Shutdown 2 in 2019-2020 already a demonstrator composed of five superchambers has been installed during the Extended Year-End Technical Stop at the beginning of 2017. Its goal is to test the system’s operational conditions and also to demonstrate the integration of the GE1/1 chambers into the CMS online system. The status of the installation and commissioning of the GE1/1 demonstrator is presented.

Performance of the CMS precision electromagnetic calorimeter at LHC Run II and prospects for High-Luminosity LHC

NASA Astrophysics Data System (ADS)

Zhang, Zhicai

2018-04-01

Many physics analyses using the Compact Muon Solenoid (CMS) detector at the LHC require accurate, high-resolution electron and photon energy measurements. Following the excellent performance achieved during LHC Run I at center-of-mass energies of 7 and 8 TeV, the CMS electromagnetic calorimeter (ECAL) is operating at the LHC with proton-proton collisions at 13 TeV center-of-mass energy. The instantaneous luminosity delivered by the LHC during Run II has achieved unprecedented levels. The average number of concurrent proton-proton collisions per bunch-crossing (pileup) has reached up to 40 interactions in 2016 and may increase further in 2017. These high pileup levels necessitate a retuning of the ECAL readout and trigger thresholds and reconstruction algorithms. In addition, the energy response of the detector must be precisely calibrated and monitored. We present new reconstruction algorithms and calibration strategies that were implemented to maintain the excellent performance of the CMS ECAL throughout Run II. We will show performance results from the 2015-2016 data taking periods and provide an outlook on the expected Run II performance in the years to come. Beyond the LHC, challenging running conditions for CMS are expected after the High-Luminosity upgrade of the LHC (HL-LHC) . We review the design and R&D studies for the CMS ECAL and present first test beam studies. Particular challenges at HL-LHC are the harsh radiation environment, the increasing data rates, and the extreme level of pile-up events, with up to 200 simultaneous proton-proton collisions. We present test beam results of hadron irradiated PbWO crystals up to fluences expected at the HL-LHC . We also report on the R&D for the new readout and trigger electronics, which must be upgraded due to the increased trigger and latency requirements at the HL-LHC.

Scheduling and Delivering Aircraft to Departure Fixes in the NY Metroplex with Controller-Managed Spacing Tools

NASA Technical Reports Server (NTRS)

Chevalley, Eric; Parke, Bonny; Kraut, Josh M.; Bienert, Nancy; Omar, Faisal; Palmer, Everett A.

2015-01-01

In this paper, successful Time-Based Flow Management (TBFM) scheduling systems for arrivals are considered and adapted to apply to departures. We present a concept of operations that integrates Controller-Managed Spacing tools for departures (CMS-D) with existing tactical departure scheduling tools to coordinate demand at departure fixes in a metroplex environment. We tested our concept in a Human-in-the-Loop simulation and compared the effect of two scheduling conditions: 1) "Departure Scheduling" consisting of an emulation of the Integrated Departure and Arrival Capability (IDAC) where Towers and a Planner (Traffic Management Coordinator at the appropriate facility) coordinate aircraft scheduled takeoff times to departure fixes; and 2) "Arrival Sensitive Departure Scheduling" where, in addition, the Tower and Planner also consider arrival Scheduled Time of Arrivals (STAs) at the airport's dependent runway. Results indicate little difference between the two scheduling conditions, but a large difference between the No Tools and the two scheduling conditions with CMS-D tools. The scheduling/CMS-D tools conditions markedly reduced heading, speed clearances, and workload for controllers who were merging flows at the departure fixes. In the tool conditions, departure controllers conditioned departures earlier rather than later when aircraft were tied near the departure fixes. In the scheduling/CMS-D tools conditions, departures crossed the departure fixes 50 seconds earlier and with an 8% error rate (consisting of time ahead or behind desired time of arrival) compared to a 19% error rate in the No Tool condition. Two exploratory runs showed that similar beneficial effects can be obtained only with the CMS-D tools without scheduling takeoff times, but at the cost of a somewhat higher workload for controllers, indicating the benefits of pre-departure scheduling of aircraft with minimal delays. Hence, we found that CMS-D tools were very beneficial in the metroplex environment we tested but that further research is needed to clarify the benefits of the various scheduling approaches.

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.

Direct Hydrogel Encapsulation of Pluripotent Stem Cells Enables Ontomimetic Differentiation and Growth of Engineered Human Heart Tissues

PubMed Central

Kerscher, Petra; Turnbull, Irene C; Hodge, Alexander J; Kim, Joonyul; Seliktar, Dror; Easley, Christopher J; Costa, Kevin D; Lipke, Elizabeth A

2016-01-01

Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. Here we demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue. PMID:26826618

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Rapsyn congenital myasthenic syndrome worsened by fluoxetine.

PubMed

Visser, Amy C; Laughlin, Ruple S; Litchy, William J; Benarroch, Eduardo E; Milone, Margherita

2017-01-01

Fluoxetine is a selective serotonin reuptake inhibitor and long-lived open channel blocker of the acetylcholine receptor, often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). We report a 42-year-old woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed before and 1 month after discontinuation of fluoxetine. The 2 Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. Muscle Nerve 55: 131-135, 2017. © 2016 Wiley Periodicals, Inc.

Retention and effects of miniature transmitters in juvenile American eels

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

Mueller, Robert P.; Janak, Jill; Liss, Stephanie A.

This study was conducted to assess the effects of a non-functional acoustic micro transmitter (tag) on survival, tag loss, and swimming ability of juvenile American eels (Anguilla rostrata). The transmitter was designed for implantation through a < 3 mm opening into the body cavity of anguilliform fishes without the need for sutures. American eels used for the swimming performance study were 113–175 mm (N = 120). There were two treatment groups (tagged and non-tagged), each treatment was split into six size groups of 10 mm for testing. Potential transmitter effects on swimming performance were examined by comparing critical swimming speedsmore » (Ucrit an index of prolonged swimming performance) for tagged and non-tagged eels. There was no significant difference in Ucrit between tagged and non-tagged eels for all of the size groups tested. Median Ucrits for tagged eels ranged from 50.2 cm/s for the smallest group tested (113–119 mm) to 63.9 cm/s for fish 141–150 mm in length. Non-tagged group median Ucrits ranged from 47.2 cm/s for the smallest group to 66.9 cm/s for the 141–150 mm group. An additional 26 eels (115–208 mm) were tagged and held for 38 d (without undergoing swimming performance tests) to determine the effects on survival and tag loss. There was no mortality during the holding period and the majority of the tag loss occurred after 20 days post-tagging, which is the current projected life of the tag. Our results indicate that micro acoustic tags can be successfully implanted in juvenile American eels with no apparent impacts to swimming ability, and would be a viable option for examining eel movement patterns in river systems and near hydroelectric facilities.« less

Accreditation status and geographic location of outpatient vascular testing facilities among Medicare beneficiaries: the VALUE (Vascular Accreditation, Location & Utilization Evaluation) study.

PubMed

Rundek, Tatjana; Brown, Scott C; Wang, Kefeng; Dong, Chuanhui; Farrell, Mary Beth; Heller, Gary V; Gornik, Heather L; Hutchisson, Marge; Needleman, Laurence; Benenati, James F; Jaff, Michael R; Meier, George H; Perese, Susana; Bendick, Phillip; Hamburg, Naomi M; Lohr, Joann M; LaPerna, Lucy; Leers, Steven A; Lilly, Michael P; Tegeler, Charles; Alexandrov, Andrei V; Katanick, Sandra L

2014-10-01

There is limited information on the accreditation status and geographic distribution of vascular testing facilities in the US. The Centers for Medicare & Medicaid Services (CMS) provide reimbursement to facilities regardless of accreditation status. The aims were to: (1) identify the proportion of Intersocietal Accreditation Commission (IAC) accredited vascular testing facilities in a 5% random national sample of Medicare beneficiaries receiving outpatient vascular testing services; (2) describe the geographic distribution of these facilities. The VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study examines the proportion of IAC accredited facilities providing vascular testing procedures nationally, and the geographic distribution and utilization of these facilities. The data set containing all facilities that billed Medicare for outpatient vascular testing services in 2011 (5% CMS Outpatient Limited Data Set (LDS) file) was examined, and locations of outpatient vascular testing facilities were obtained from the 2011 CMS/Medicare Provider of Services (POS) file. Of 13,462 total vascular testing facilities billing Medicare for vascular testing procedures in a 5% random Outpatient LDS for the US in 2011, 13% (n=1730) of facilities were IAC accredited. The percentage of IAC accredited vascular testing facilities in the LDS file varied significantly by US region, p<0.0001: 26%, 12%, 11%, and 7% for the Northeast, South, Midwest, and Western regions, respectively. Findings suggest that the proportion of outpatient vascular testing facilities that are IAC accredited is low and varies by region. Increasing the number of accredited vascular testing facilities to improve test quality is a hypothesis that should be tested in future research. © The Author(s) 2014.

Drug Screening Using a Library of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals Disease Specific Patterns of Cardiotoxicity

PubMed Central

Liang, Ping; Lan, Feng; Lee, Andrew S.; Gong, Tingyu; Sanchez-Freire, Veronica; Wang, Yongming; Diecke, Sebastian; Sallam, Karim; Knowles, Joshua W.; Wang, Paul J.; Nguyen, Patricia K.; Bers, Donald M.; Robbins, Robert C.; Wu, Joseph C.

2013-01-01

Background Cardiotoxicity is a leading cause for drug attrition during pharmaceutical development and has resulted in numerous preventable patient deaths. Incidents of adverse cardiac drug reactions are more common in patients with pre-existing heart disease than the general population. Here we generated a library of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with various hereditary cardiac disorders to model differences in cardiac drug toxicity susceptibility for patients of different genetic backgrounds. Methods and Results Action potential duration (APD) and drug-induced arrhythmia were measured at the single cell level in hiPSC-CMs derived from healthy subjects and patients with hereditary long QT syndrome (LQT), familial hypertrophic cardiomyopathy (HCM), and familial dilated cardiomyopathy (DCM). Disease phenotypes were verified in LQT, HCM, and DCM iPSC-CMs by immunostaining and single cell patch clamp. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and the human ether-a-go-go-related gene (hERG) expressing human embryonic kidney (HEK293) cells were used as controls. Single cell PCR confirmed expression of all cardiac ion channels in patient-specific hiPSC-CMs as well as hESC-CMs, but not in HEK293 cells. Disease-specific hiPSC-CMs demonstrated increased susceptibility to known cardiotoxic drugs as measured by APD and quantification of drug-induced arrhythmias such as early after depolarizations (EADs) and delayed after depolarizations (DADs). Conclusions We have recapitulated drug-induced cardiotoxicity profiles for healthy subjects, LQT, HCM, and DCM patients at the single cell level for the first time. Our data indicate that healthy and diseased individuals exhibit different susceptibilities to cardiotoxic drugs and that use of disease-specific hiPSC-CMs may predict adverse drug responses more accurately than standard hERG test or healthy control hiPSC-CM/hESC-CM screening assays. PMID:23519760

Rose oil (from Rosa × damascena Mill.) vapor attenuates depression-induced oxidative toxicity in rat brain.

PubMed

Nazıroğlu, Mustafa; Kozlu, Süleyman; Yorgancıgil, Emre; Uğuz, Abdülhadi Cihangir; Karakuş, Kadir

2013-01-01

Oxidative stress is a critical route of damage in various physiological stress-induced disorders, including depression. Rose oil may be a useful treatment for depression because it contains flavonoids which include free radical antioxidant compounds such as rutin and quercetin. We investigated the effects of absolute rose oil (from Rosa × damascena Mill.) and experimental depression on lipid peroxidation and antioxidant levels in the cerebral cortex of rats. Thirty-two male rats were randomly divided into four groups. The first group was used as control, while depression was induced in the second group using chronic mild stress (CMS). Oral (1.5 ml/kg) and vapor (0.15 ml/kg) rose oil were given for 28 days to CMS depression-induced rats, constituting the third and fourth groups, respectively. The sucrose preference test was used weekly to identify depression-like phenotypes during the experiment. At the end of the experiment, cerebral cortex samples were taken from all groups. The lipid peroxidation levels in the cerebral cortex in the CMS group were higher than in control whereas their levels were decreased by rose oil vapor exposure. The vitamin A, vitamin E, vitamin C and β-carotene concentrations in the cerebral cortex were lower in the CMS group than in the control group whereas their concentrations were higher in the rose oil vapor plus CMS group. The CMS-induced antioxidant vitamin changes were not modulated by oral treatment. Glutathione peroxidase activity and reduced glutathione did not change statistically in the four groups following CMS or either treatment. In conclusion, experimental depression is associated with elevated oxidative stress while treatment with rose oil vapor induced protective effects on oxidative stress in depression.

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

PubMed

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

2015-12-01

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

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

PubMed Central

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

2015-01-01

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

42 CFR 493.803 - Condition: Successful participation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... testing performance. (3) The laboratory has a poor compliance history. [57 FR 7146, Feb. 28, 1992, as... testing program, for the initial unsuccessful performance, CMS may direct the laboratory to undertake...

Are Evidence-based Practices Associated With Effective Prevention of Hospital-acquired Pressure Ulcers in US Academic Medical Centers?

PubMed

Padula, William V; Gibbons, Robert D; Valuck, Robert J; Makic, Mary B F; Mishra, Manish K; Pronovost, Peter J; Meltzer, David O

2016-05-01

In 2008, the Centers for Medicare and Medicaid Services (CMS) established nonpayment policies resulting from costliness of hospital-acquired pressure ulcers (HAPUs) to hospitals. This prompted hospitals to adopt quality improvement (QI) interventions that increase use of evidence-based practices (EBPs) for HAPU prevention. To evaluate the longitudinal impact of CMS policy and QI adoption on HAPU rates. We characterized longitudinal adoption of 25 QI interventions that support EBPs through hospital leadership, staff, information technology, and performance and improvement. Quarterly counts of HAPU incidence and inpatient characteristics were collected from 55 University HealthSystem Consortium hospitals between 2007 and 2012. Mixed-effects regression models tested the longitudinal association of CMS policy, HAPU coding, and QI on HAPU rates. The models assumed level-2 random intercepts and random effects for CMS policy and EBP implementation to account for between-hospital variability in HAPU incidence. Controlling for all 25 QI interventions, specific updates to EBPs for HAPU prevention had a significant, though modest reduction on HAPU rates (-1.86 cases/quarter; P=0.002) and the effect of CMS nonpayment policy on HAPU prevention was much greater (-11.32 cases/quarter; P<0.001). HAPU rates were significantly lower after changes in CMS reimbursement. Reductions are associated with hospital-wide implementation of EBPs for HAPU prevention. Given that administrative data were used, it remains unknown whether these improvements were due to changes in coding or improved quality of care.

Are Evidence-based Practices Associated with Effective Prevention of Hospital-acquired Pressure Ulcers in U.S. Academic Medical Centers?

PubMed Central

Padula, William V.; Gibbons, Robert D.; Valuck, Robert J.; Makic, Mary Beth F.; Mishra, Manish K.; Pronovost, Peter J.; Meltzer, David O.

2016-01-01

Background In 2008, the Centers for Medicare and Medicaid Services (CMS) established nonpayment policies resulting from costliness of hospital-acquired pressure ulcers (HAPUs) to hospitals. This prompted hospitals to adopt quality improvement (QI) interventions that increase use of evidence-based practices (EBPs) for HAPU prevention. Objective To evaluate the longitudinal impact of CMS policy and QI adoption on HAPU rates. Methods We characterized longitudinal adoption of 25 QI interventions that support EBPs through hospital leadership, staff, information technology, and performance and improvement. Quarterly counts of HAPU incidence and inpatient characteristics were collected from 55 UHC hospitals between 2007–2012. Mixed-effects regression models tested the longitudinal association of CMS policy, HAPU coding and QI on HAPU rates. The models assumed level-2 random-intercepts and random effects for CMS policy and EBP implementation to account for between-hospital variability in HAPU incidence. Results Controlling for all 25 QI interventions, specific updates to EBPs for HAPU prevention had a significant, though modest reduction on HAPU rates (−1.86 cases/quarter; p=0.002) and the effect of CMS nonpayment policy on HAPU prevention was much greater (−11.32 cases/quarter; p<0.001). Conclusions HAPU rates were significantly lower following changes in CMS reimbursement. Reductions are associated with hospital-wide implementation of EBPs for HAPU prevention. Given that administrative data were used, it remains unknown whether these improvements were due to changes in coding or improved quality of care. PMID:27078824

Consequences of a double hit of stress during the perinatal period and midlife in female rats: Mismatch or cumulative effect?

PubMed

Van Camp, Gilles; Cigalotti, Jenny; Bouwalerh, Hammou; Mairesse, Jérôme; Gatta, Eleonora; Palanza, Paola; Maccari, Stefania; Morley-Fletcher, Sara

2018-07-01

The interplay between experiences during critical developmental periods and later adult life is crucial in shaping individual variability in stress coping strategies. Exposure to stressful events in early life has strongly programs an individual's phenotype and adaptive capabilities. Until now, studies on programming and reversal strategies in early life stress animal models have been essentially limited to males. By using the perinatal stress (PRS) rat model (a model more sensitive to aging changes) in middle-aged females, we investigated the behavioral and endocrine responses following exposure in later life to an unpredictable chronic mild stress (uCMS) condition for six weeks. PRS by itself accelerated the ageing-related-disruption in the estrous cycle and led to reductions in the levels of estradiol. It also reduced motivational and risk-taking behavior in later life, with PRS females being characterized by a reduction in self-grooming in the splash test, in the exploration of the light compartment in the light/dark box test and in the time spent eating a palatable food in the novelty-induced suppression feeding test. PRS females showed impaired regulation of plasma glucose and insulin levels following a glucose challenge, with a hyperglycemic phenotype, and disrupted feedback of the HPA axis after acute stress with respect to controls. Remarkably, all PRS-induced alterations were modified by exposure to the uCMS procedure, thus resulting in a disease-dependent intervention; controls were not affected by uCMS, except for a slight and transient reduction in body weight, while PRS females displayed a reduced body weight gain for the entire duration of the uCMS procedure. Interestingly, the effects of uCMS on PRS females were still observed up to two months after its termination and the females displayed heightened rhythms of locomotor activity and enhanced sensitivity to reward with respect to controls exposed to uCMS. Our findings indicate that many parameters of the PRS female adult phenotype are shaped by both early and later life experiences in a non-additive way. As a consequence, early stressed individuals may be programmed with a more dynamic phenotype than non-stressed individuals. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Testing the 2-TeV resonance with trileptons

DOE PAGES

Das, Arindam; Nagata, Natsumi; Okada, Nobuchika

2016-03-09

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

Screening drug-induced arrhythmia [corrected] using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays.

PubMed

Navarrete, Enrique G; Liang, Ping; Lan, Feng; Sanchez-Freire, Verónica; Simmons, Chelsey; Gong, Tingyu; Sharma, Arun; Burridge, Paul W; Patlolla, Bhagat; Lee, Andrew S; Wu, Haodi; Beygui, Ramin E; Wu, Sean M; Robbins, Robert C; Bers, Donald M; Wu, Joseph C

2013-09-10

Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell-derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls. We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.

76 FR 5804 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

.../ operators to submit cost data and provide copies of recent emissions test reports and continuous emission... purposes of the regulatory reviews. The emissions test data (test reports, CEMS data, and CMS data...

B physics and Quarkonia in CMS

NASA Astrophysics Data System (ADS)

Fiorendi, Sara

2017-12-01

The heavy-flavor sector offers the opportunity to perform indirect tests of beyond the Standard Model physics through precision measurements and of quantum chromodynamics (QCD) through particle production studies. A review of recent measurements on heavy flavors from the CMS experiment is presented. Results are based on data collected during LHC Run I and Run II and include measurements of heavy flavor production and properties, rare decays, CP violation, exotic and standard quarkonia. Warning, no authors found for 2017EPJWC.16407006.

An expert system prototype for aiding in the development of software functional requirements for NASA Goddard's command management system: A case study and lessons learned

NASA Technical Reports Server (NTRS)

Liebowitz, Jay

1986-01-01

At NASA Goddard, the role of the command management system (CMS) is to transform general requests for spacecraft opeerations into detailed operational plans to be uplinked to the spacecraft. 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. Presently, it takes one to three years, with meetings once or twice a week, to determine functional requirements for CMS software design. As an alternative approach to the present technique of developing CMS software functional requirements, an expert system prototype was developed to aid in this function. Specifically, the knowledge base was formulated through interactions with domain experts, and was then linked to an existing expert system application generator called 'Knowledge Engineering System (Version 1.3).' Knowledge base development focused on four major steps: (1) develop the problem-oriented attribute hierachy; (2) determine the knowledge management approach; (3) encode the knowledge base; and (4) validate, test, certify, and evaluate the knowledge base and the expert system prototype as a whole. Backcasting was accomplished for validating and testing the expert system prototype. Knowledge refinement, evaluation, and implementation procedures of the expert system prototype were then transacted.

Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

PubMed

Lu, Yanxia; Ho, Cyrus S; Liu, Xin; Chua, Anna N; Wang, Wei; McIntyre, Roger S; Ho, Roger C

2017-01-01

This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05). There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

Selfish evolution of cytonuclear hybrid incompatibility in Mimulus

PubMed Central

Finseth, Findley R.; Barr, Camille M.; Fishman, Lila

2016-01-01

Intraspecific coevolution between selfish elements and suppressors may promote interspecific hybrid incompatibility, but evidence of this process is rare. Here, we use genomic data to test alternative models for the evolution of cytonuclear hybrid male sterility in Mimulus. In hybrids between Iron Mountain (IM) Mimulus guttatus × Mimulus nasutus, two tightly linked M. guttatus alleles (Rf1/Rf2) each restore male fertility by suppressing a local mitochondrial male-sterility gene (IM-CMS). Unlike neutral models for the evolution of hybrid incompatibility loci, selfish evolution predicts that the Rf alleles experienced strong selection in the presence of IM-CMS. Using whole-genome sequences, we compared patterns of population-genetic variation in Rf at IM to a neighbouring population that lacks IM-CMS. Consistent with local selection in the presence of IM-CMS, the Rf region shows elevated FST, high local linkage disequilibrium and a distinct haplotype structure at IM, but not at Cone Peak (CP), suggesting a recent sweep in the presence of IM-CMS. In both populations, Rf2 exhibited lower polymorphism than other regions, but the low-diversity outliers were different between CP and IM. Our results confirm theoretical predictions of ubiquitous cytonuclear conflict in plants and provide a population-genetic mechanism for the evolution of a common form of hybrid incompatibility. PMID:27629037

Comparison of the accuracy of maxillary position between conventional model surgery and virtual surgical planning.

PubMed

Ritto, F G; Schmitt, A R M; Pimentel, T; Canellas, J V; Medeiros, P J

2018-02-01

The aim of this study was to determine whether virtual surgical planning (VSP) is an accurate method for positioning the maxilla when compared to conventional articulator model surgery (CMS), through the superimposition of computed tomography (CT) images. This retrospective study included the records of 30 adult patients submitted to bimaxillary orthognathic surgery. Two groups were created according to the treatment planning performed: CMS and VSP. The treatment planning protocol was the same for all patients. Pre- and postoperative CT images were superimposed and the linear distances between upper jaw reference points were measured. Measurements were then compared to the treatment planning, and the difference in accuracy between CMS and VSP was determined using the t-test for independent samples. The success criterion adopted was a mean linear difference of <2mm. The mean linear difference between planned and obtained movements for CMS was 1.27±1.05mm, and for VSP was 1.20±1.08mm. With CMS, 80% of overlapping reference points had a difference of <2mm, while for VSP this value was 83.6%. There was no statistically significant difference between the two techniques regarding accuracy (P>0.05). Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Selfish evolution of cytonuclear hybrid incompatibility in Mimulus.

PubMed

Case, Andrea L; Finseth, Findley R; Barr, Camille M; Fishman, Lila

2016-09-14

Intraspecific coevolution between selfish elements and suppressors may promote interspecific hybrid incompatibility, but evidence of this process is rare. Here, we use genomic data to test alternative models for the evolution of cytonuclear hybrid male sterility in Mimulus In hybrids between Iron Mountain (IM) Mimulus guttatus × Mimulus nasutus, two tightly linked M. guttatus alleles (Rf1/Rf2) each restore male fertility by suppressing a local mitochondrial male-sterility gene (IM-CMS). Unlike neutral models for the evolution of hybrid incompatibility loci, selfish evolution predicts that the Rf alleles experienced strong selection in the presence of IM-CMS. Using whole-genome sequences, we compared patterns of population-genetic variation in Rf at IM to a neighbouring population that lacks IM-CMS. Consistent with local selection in the presence of IM-CMS, the Rf region shows elevated FST, high local linkage disequilibrium and a distinct haplotype structure at IM, but not at Cone Peak (CP), suggesting a recent sweep in the presence of IM-CMS. In both populations, Rf2 exhibited lower polymorphism than other regions, but the low-diversity outliers were different between CP and IM. Our results confirm theoretical predictions of ubiquitous cytonuclear conflict in plants and provide a population-genetic mechanism for the evolution of a common form of hybrid incompatibility. © 2016 The Author(s).

Protective effects of chronic mild stress during adolescence in the low-novelty responder rat.

PubMed

Rana, Samir; Nam, Hyungwoo; Glover, Matthew E; Akil, Huda; Watson, Stanley J; Clinton, Sarah M; Kerman, Ilan A

2016-01-01

Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats.

Renal sympathetic denervation increases renal blood volume per cardiac cycle: a serial magnetic resonance imaging study in resistant hypertension.

PubMed

Delacroix, Sinny; Chokka, Ramesh G; Nelson, Adam J; Wong, Dennis T; Sidharta, Samuel; Pederson, Stephen M; Rajwani, Adil; Nimmo, Joanne; Teo, Karen S; Worthley, Stephen G

2017-01-01

Preclinical studies have demonstrated improvements in renal blood flow after renal sympathetic denervation (RSDN); however, such effects are yet to be confirmed in patients with resistant hypertension. Herein, we assessed the effects of RSDN on renal artery blood flow and diameter at multiple time points post-RSDN. Patients (n=11) with systolic blood pressures ≥160 mmHg despite taking three or more antihypertensive medications at maximum tolerated dose were recruited into this single-center, prospective, non-blinded study. Magnetic resonance imaging indices included renal blood flow and renal artery diameters at baseline, 1 month and 6 months. In addition to significant decreases in blood pressures ( p <0.0001), total volume of blood flow per cardiac cycle increased by 20% from 6.9±2 mL at baseline to 8.4±2 mL ( p =0.003) at 1 month and to 8.0±2 mL ( p =0.04) 6 months post-procedure, with no changes in the renal blood flow. There was a significant decrease in renal artery diameters from 7±2 mm at baseline to 6±1 mm ( p =0.03) at 1 month post-procedure. This decrease was associated with increases in maximum velocity of blood flow from 73±20 cm/s at baseline to 78±19 cm/s at 1 month post-procedure. Notably, both parameters reverted to 7±2 mm and 72±18 cm/s, respectively, 6 months after procedure. RSDN improves renal physiology as evidenced by significant improvements in total volume of blood flow per cardiac cycle. Additionally, for the first time, we identified a transient decrease in renal artery diameters immediately after procedure potentially caused by edema and inflammation that reverted to baseline values 6 months post-procedure.

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.

Evolution of permeability and Biot coefficient at high mean stresses in high porosity sandstone

DOE PAGES

Ingraham, Mathew D.; Bauer, Stephen J.; Issen, Kathleen A.; ...

2017-05-01

A series of constant mean stress (CMS) and constant shear stress (CSS) tests were performed to investigate the evolution of permeability and Biot coefficient at high mean stresses in a high porosity reservoir analog (Castlegate sandstone). Permeability decreases as expected with increasing mean stress, from about 20 Darcy at the beginning of the tests to between 1.5 and 0.3 Darcy at the end of the tests (mean stresses up to 275 MPa). The application of shear stress causes permeability to drop below that of a hydrostatic test at the same mean stress. Results show a nearly constant rate decrease inmore » the Biot coefficient as the mean stress increases during hydrostatic loading, and as the shear stress increases during CMS loading. In conclusion, CSS tests show a stabilization of the Biot coefficient after the application of shear stress.« less

Evolution of permeability and Biot coefficient at high mean stresses in high porosity sandstone

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

Ingraham, Mathew D.; Bauer, Stephen J.; Issen, Kathleen A.

A series of constant mean stress (CMS) and constant shear stress (CSS) tests were performed to investigate the evolution of permeability and Biot coefficient at high mean stresses in a high porosity reservoir analog (Castlegate sandstone). Permeability decreases as expected with increasing mean stress, from about 20 Darcy at the beginning of the tests to between 1.5 and 0.3 Darcy at the end of the tests (mean stresses up to 275 MPa). The application of shear stress causes permeability to drop below that of a hydrostatic test at the same mean stress. Results show a nearly constant rate decrease inmore » the Biot coefficient as the mean stress increases during hydrostatic loading, and as the shear stress increases during CMS loading. In conclusion, CSS tests show a stabilization of the Biot coefficient after the application of shear stress.« less

Radioactive source calibration test of the CMS Hadron Endcap Calorimeter test wedge with Phase I upgrade electronics

NASA Astrophysics Data System (ADS)

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

2017-12-01

The Phase I upgrade of the CMS Hadron Endcap Calorimeters consists of new photodetectors (Silicon Photomultipliers in place of Hybrid Photo-Diodes) and front-end electronics. The upgrade will eliminate the noise and the calibration drift of the Hybrid Photo-Diodes and enable the mitigation of the radiation damage of the scintillators and the wavelength shifting fibers with a larger spectral acceptance of the Silicon Photomultipliers. The upgrade also includes increased longitudinal segmentation of the calorimeter readout, which allows pile-up mitigation and recalibration due to depth-dependent radiation damage. As a realistic operational test, the responses of the Hadron Endcap Calorimeter wedges were calibrated with a 60Co radioactive source with upgrade electronics. The test successfully established the procedure for future source calibrations of the Hadron Endcap Calorimeters. Here we describe the instrumentation details and the operational experiences related to the sourcing test.

Comparing surgical repair with conservative treatment for degenerative rotator cuff tears: a randomized controlled trial.

PubMed

Lambers Heerspink, Frederik O; van Raay, Jos J A M; Koorevaar, Rinco C T; van Eerden, Pepijn J M; Westerbeek, Robin E; van 't Riet, Esther; van den Akker-Scheek, Inge; Diercks, Ronald L

2015-08-01

Good clinical results have been reported for both surgical and conservative treatment of rotator cuff tears. The primary aim of this randomized controlled trial was to compare functional and radiologic improvement after surgical and conservative treatment of degenerative rotator cuff tears. We conducted a randomized controlled trial that included 56 patients with a degenerative full-thickness rotator cuff tear between January 2009 and December 2012; 31 patients were treated conservatively, and rotator cuff repair was performed in 25 patients. Outcome measures, including the Constant-Murley score (CMS), visual analog scale (VAS) pain and VAS disability scores, were assessed preoperatively and after 6 weeks and 3, 6, and 12 months. Magnetic resonance imaging was performed preoperatively and at 12 months postoperatively. At 12 months postoperatively, the mean CMS was 81.9 (standard deviation [SD], 15.6) in the surgery group vs 73.7 (SD, 18.4) in the conservative group (P = .08). VAS pain (P = .04) and VAS disability (P = .02) were significantly lower in the surgery group at the 12-month follow-up. A subgroup analysis showed postoperative CMS results were significantly better in surgically treated patients without a retear compared with conservatively treated patients (88.5 [SD, 6.2] vs 73.7 [SD, 18.4]). In our population of patients with degenerative rotator cuff tears who were randomly treated by surgery or conservative protocol, we did not observe differences in functional outcome as measured with the CMS 1 year after treatment. However, significant differences in pain and disabilities were observed in favor of surgical treatment. The best outcomes in function and pain were seen in patients with an intact rotator cuff postoperatively. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

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.

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...

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.

A conflict management scale for pharmacy.

PubMed

Austin, Zubin; Gregory, Paul A; Martin, Craig

2009-11-12

To develop and establish the validity and reliability of a conflict management scale specific to pharmacy practice and education. A multistage inventory-item development process was undertaken involving 93 pharmacists and using a previously described explanatory model for conflict in pharmacy practice. A 19-item inventory was developed, field tested, and validated. The conflict management scale (CMS) demonstrated an acceptable degree of reliability and validity for use in educational or practice settings to promote self-reflection and self-awareness regarding individuals' conflict management styles. The CMS provides a unique, pharmacy-specific method for individuals to determine and reflect upon their own conflict management styles. As part of an educational program to facilitate self-reflection and heighten self-awareness, the CMS may be a useful tool to promote discussions related to an important part of pharmacy practice.

42 CFR 493.1236 - Standard: Evaluation of proficiency testing performance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the following: (1) Any analyte or subspecialty without analytes listed in subpart I of this part that is not evaluated or scored by a CMS-approved proficiency testing program. (2) Any analyte, specialty...

42 CFR 493.1236 - Standard: Evaluation of proficiency testing performance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the following: (1) Any analyte or subspecialty without analytes listed in subpart I of this part that is not evaluated or scored by a CMS-approved proficiency testing program. (2) Any analyte, specialty...

42 CFR 493.1236 - Standard: Evaluation of proficiency testing performance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the following: (1) Any analyte or subspecialty without analytes listed in subpart I of this part that is not evaluated or scored by a CMS-approved proficiency testing program. (2) Any analyte, specialty...

42 CFR 493.1236 - Standard: Evaluation of proficiency testing performance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the following: (1) Any analyte or subspecialty without analytes listed in subpart I of this part that is not evaluated or scored by a CMS-approved proficiency testing program. (2) Any analyte, specialty...

42 CFR 493.1236 - Standard: Evaluation of proficiency testing performance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the following: (1) Any analyte or subspecialty without analytes listed in subpart I of this part that is not evaluated or scored by a CMS-approved proficiency testing program. (2) Any analyte, specialty...

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.

Forward and small-x QCD physics results from CMS experiment at LHC

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

Cerci, Deniz Sunar, E-mail: deniz.sunar.cerci@cern.ch

2016-03-25

The Compact Muon Solenoid (CMS) is one of the two large, multi-purpose experiments at the Large Hadron Collider (LHC) at CERN. During the Run I Phase a large pp collision dataset has been collected and the CMS collaboration has explored measurements that shed light on a new era. Forward and small-x quantum chromodynamics (QCD) physics measurements with CMS experiment covers a wide range of physics subjects. Some of highlights in terms of testing the very low-x QCD, underlying event and multiple interaction characteristics, photon-mediated processes, jets with large rapidity separation at high pseudo-rapidities and the inelastic proton-proton cross section dominatedmore » by diffractive interactions are presented. Results are compared to Monte Carlo (MC) models with different parameter tunes for the description of the underlying event and to perturbative QCD calculations. The prominent role of multi-parton interactions has been confirmed in the semihard sector but no clear deviation from the standard Dglap parton evolution due to Bfkl has been observed. An outlook to the prospects at 13 TeV is given.« less

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.

Mixed Matrix Carbon Molecular Sieve and Alumina (CMS-Al2O3) Membranes

NASA Astrophysics Data System (ADS)

Song, Yingjun; Wang, David K.; Birkett, Greg; Martens, Wayde; Duke, Mikel C.; Smart, Simon; Diniz da Costa, João C.

2016-07-01

This work shows mixed matrix inorganic membranes prepared by the vacuum-assisted impregnation method, where phenolic resin precursors filled the pore of α-alumina substrates. Upon carbonisation, the phenolic resin decomposed into several fragments derived from the backbone of the resin matrix. The final stages of decomposition (>650 °C) led to a formation of carbon molecular sieve (CMS) structures, reaching the lowest average pore sizes of ~5 Å at carbonisation temperatures of 700 °C. The combination of vacuum-assisted impregnation and carbonisation led to the formation of mixed matrix of CMS and α-alumina particles (CMS-Al2O3) in a single membrane. These membranes were tested for pervaporative desalination and gave very high water fluxes of up to 25 kg m-2 h-1 for seawater (NaCl 3.5 wt%) at 75 °C. Salt rejection was also very high varying between 93-99% depending on temperature and feed salt concentration. Interestingly, the water fluxes remained almost constant and were not affected as feed salt concentration increased from 0.3, 1 and 3.5 wt%.

Mixed Matrix Carbon Molecular Sieve and Alumina (CMS-Al2O3) Membranes.

PubMed

Song, Yingjun; Wang, David K; Birkett, Greg; Martens, Wayde; Duke, Mikel C; Smart, Simon; Diniz da Costa, João C

2016-07-29

This work shows mixed matrix inorganic membranes prepared by the vacuum-assisted impregnation method, where phenolic resin precursors filled the pore of α-alumina substrates. Upon carbonisation, the phenolic resin decomposed into several fragments derived from the backbone of the resin matrix. The final stages of decomposition (>650 °C) led to a formation of carbon molecular sieve (CMS) structures, reaching the lowest average pore sizes of ~5 Å at carbonisation temperatures of 700 °C. The combination of vacuum-assisted impregnation and carbonisation led to the formation of mixed matrix of CMS and α-alumina particles (CMS-Al2O3) in a single membrane. These membranes were tested for pervaporative desalination and gave very high water fluxes of up to 25 kg m(-2) h(-1) for seawater (NaCl 3.5 wt%) at 75 °C. Salt rejection was also very high varying between 93-99% depending on temperature and feed salt concentration. Interestingly, the water fluxes remained almost constant and were not affected as feed salt concentration increased from 0.3, 1 and 3.5 wt%.

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

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

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

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

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.

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

DOE PAGES

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

2017-05-30

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

Qualification and calibration tests of detector modules for the CMS Pixel Phase 1 upgrade

NASA Astrophysics Data System (ADS)

Zhu, D.; Backhaus, M.; Berger, P.; Meinhard, M.; Starodumov, A.; Tavolaro, V.

2018-01-01

In high energy particle physics, accelerator- and detector-upgrades always go hand in hand. The instantaneous luminosity of the Large Hadron Collider will increase to up to L = 2×1034cm-2s-1 during Run 2 until 2023. In order to cope with such luminosities, the pixel detector of the CMS experiment has been replaced early 2017. The so-called CMS Pixel phase 1 upgrade detector consists of 1184 modules with new design. An important production step is the module qualification and calibration, ensuring their proper functionality within the detector. This paper summarizes the qualification and calibration tests and results of modules used in the innermost two detector layers with focus on methods using module-internal calibration signals. Extended characterizations on pixel level such as electronic noise and bump bond connectivity, optimization of operational parameters, sensor quality and thermal stress resistance were performed using a customized setup with controlled environment. It could be shown that the selected modules have on average 0.55‰ ± 0.01‰ defective pixels and that all performance parameters stay within their specifications.

CRISPR correction of the PRKAG2 gene mutation in the patient's induced pluripotent stem cell-derived cardiomyocytes eliminates electrophysiological and structural abnormalities.

PubMed

Ben Jehuda, Ronen; Eisen, Binyamin; Shemer, Yuval; Mekies, Lucy N; Szantai, Agnes; Reiter, Irina; Cui, Huanhuan; Guan, Kaomei; Haron-Khun, Shiraz; Freimark, Dov; Sperling, Silke R; Gherghiceanu, Mihaela; Arad, Michael; Binah, Ofer

2018-02-01

Mutations in the PRKAG2 gene encoding the γ-subunit of adenosine monophosphate kinase (AMPK) cause hypertrophic cardiomyopathy (HCM) and familial Wolff-Parkinson-White (WPW) syndrome. Patients carrying the R302Q mutation in PRKAG2 present with sinus bradycardia, escape rhythms, ventricular preexcitation, supraventricular tachycardia, and atrioventricular block. This mutation affects AMPK activity and increases glycogen storage in cardiomyocytes. The link between glycogen storage, WPW syndrome, HCM, and arrhythmias remains unknown. The purpose of this study was to investigate the pathological changes caused by the PRKAG2 mutation. We tested the hypothesis that patient's induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) display clinical aspects of the disease. Using clustered regularly interspaced short palindromic repeats (CRISPR) technology, we corrected the mutation and then generated isogenic iPSC-CMs. Action potentials were recorded from spontaneously firing and paced cardiomyocytes using the patch clamp technique. Using a microelectrode array setup, we recorded electrograms from iPSC-CMs clusters. Transmission electron microscopy was used to detect ultrastructural abnormalities in the mutated iPSC-CMs. PRKAG2-mutated iPSC-CMs exhibited abnormal firing patterns, delayed afterdepolarizations, triggered arrhythmias, and augmented beat rate variability. Importantly, CRISPR correction eliminated the electrophysiological abnormalities, the augmented glycogen, storage, and cardiomyocyte hypertrophy. PRKAG2-mutated iPSC-CMs displayed functional and structural abnormalities, which were abolished by correcting the mutation in the patient's iPSCs using CRISPR technology. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices

PubMed Central

Morrison, Tina M.; Dreher, Maureen L.; Nagaraja, Srinidhi; Angelone, Leonardo M.; Kainz, Wolfgang

2018-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making. PMID:29479395

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices.

PubMed

Morrison, Tina M; Dreher, Maureen L; Nagaraja, Srinidhi; Angelone, Leonardo M; Kainz, Wolfgang

2017-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making.

Bundle Payment Program Initiative: Roles of a Nurse Navigator and Home Health Professionals.

PubMed

Peiritsch, Heather

2017-06-01

With the passage of the Affordable Care Act, The Centers for Medicare and Medicaid (CMS) introduced a new value-based payment model, the Bundle Payment Care Initiative. The CMS Innovation (Innovation Center) authorized hospitals to participate in a pilot to test innovative payment and service delivery models that have a potential to reduce Medicare expenditures while maintaining or improving the quality of care for beneficiaries. A hospital-based home care agency, Abington Jefferson Health Home Care Department, led the initiative for the development and implementation of the Bundled Payment Program. This was a creative and innovative method to improve care along the continuum while testing a value-based care model.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

PubMed

Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

2017-11-01

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

47 CFR 10.350 - CMAS Testing requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... later than the date of deployment of the CMAS, of CMAS components. (a) Required monthly tests. Testing... a required monthly test (RMT) message initiated by the Federal Alert Gateway Administrator. (2... maintenance windows. (3) A Participating CMS Provider may forego an RMT if the RMT is pre-empted by actual...

40 CFR 63.8 - Monitoring requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... with conducting performance tests under § 63.7. Verification of operational status shall, at a minimum... in the relevant standard; or (B) The CMS fails a performance test audit (e.g., cylinder gas audit), relative accuracy audit, relative accuracy test audit, or linearity test audit; or (C) The COMS CD exceeds...

40 CFR 63.8 - Monitoring requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... with conducting performance tests under § 63.7. Verification of operational status shall, at a minimum... in the relevant standard; or (B) The CMS fails a performance test audit (e.g., cylinder gas audit), relative accuracy audit, relative accuracy test audit, or linearity test audit; or (C) The COMS CD exceeds...

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

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

Kwan, Simon; Lei, CM; Menasce, Dario

An all silicon pixel telescope has been assembled and used at the Fermilab Test Beam Facility (FTBF) since 2009 to provide precise tracking information for different test beam experiments with a wide range of Detectors Under Test (DUTs) requiring high resolution measurement of the track impact point. The telescope is based on CMS pixel modules left over from the CMS forward pixel production. Eight planes are arranged to achieve a resolution of less than 8 μm on the 120 GeV proton beam transverse coordinate at the DUT position. In order to achieve such resolution with 100 × 150 μm 2more » pixel cells, the planes were tilted to 25 degrees to maximize charge sharing between pixels. Crucial for obtaining this performance is the alignment software, called Monicelli, specifically designed and optimized for this system. This paper will describe the telescope hardware, the data acquisition system and the alignment software constituting this particle tracking system for test beam users.« less

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

PubMed

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

2016-07-01

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

Store-and-feedforward adaptive gaming system for hand-finger motion tracking in telerehabilitation.

PubMed

Lockery, Daniel; Peters, James F; Ramanna, Sheela; Shay, Barbara L; Szturm, Tony

2011-05-01

This paper presents a telerehabilitation system that encompasses a webcam and store-and-feedforward adaptive gaming system for tracking finger-hand movement of patients during local and remote therapy sessions. Gaming-event signals and webcam images are recorded as part of a gaming session and then forwarded to an online healthcare content management system (CMS) that separates incoming information into individual patient records. The CMS makes it possible for clinicians to log in remotely and review gathered data using online reports that are provided to help with signal and image analysis using various numerical measures and plotting functions. Signals from a 6 degree-of-freedom magnetic motion tracking system provide a basis for video-game sprite control. The MMT provides a path for motion signals between common objects manipulated by a patient and a computer game. During a therapy session, a webcam that captures images of the hand together with a number of performance metrics provides insight into the quality, efficiency, and skill of a patient.

40 CFR 63.8 - Monitoring requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... in the relevant standard; or (B) The CMS fails a performance test audit (e.g., cylinder gas audit), relative accuracy audit, relative accuracy test audit, or linearity test audit; or (C) The COMS CD exceeds...) Data recording, calculations, and reporting; (v) Accuracy audit procedures, including sampling and...

Investigation of the intestinal permeability of ciclosporin using the in situ technique in rats and the relevance of P-glycoprotein.

PubMed

Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba; Damani, Sanaz; Mehtari, Maryam

2008-01-01

The primary endpoint of this study was to determine the intestinal permeability of ciclosporin (cyclosporine A, CsA, CAS 59865-13-3) using the single-pass intestinal perfusion technique (SPIP) and a range of concentrations in rats. The second objective was to assess the quantitative contribution of P-glycoprotein (P-gp)-mediated efflux in limiting the oral bioavailability of CsA using erythromycin (Ery, CAS 114-07-8) as an inhibitor of P-gp efflux transporter. A solution containing CsA and phenol red either in the presence or in the absence of Ery as a P-gp inhibitor was perfused through a cannulated jejunal segment in rats. Outlet samples were collected every 10 min in micro tubes up to 90 min. Samples were analyzed using a modified reverse phase HPLC method. The mean effective permeability coefficients (Peff) of CsA in concentrations of 5, 10, 15 and 20 micromol/L in the perfusion solution were found to be 2.21 (+/- 0.26) x 10(-4) cm/s, 3.34 (+/- 1.29) x 10(-4) cm/s, 3.12 (+/- 0.23) x 10(-4) cm/s and 2.73 (+/- 0.28) x 10(-4) cm/s, respectively. The corresponding values in the presence of Ery were found to be 3.96 (+/- 1.04) x 10(-4) cm/s, 5.34 (+/- 1.29) x 10(-4) cm/s, 3.72 (+/- 0.21) x 10(-4) cm/s and 4.41 (+/- 0.89) x 10(-4) cm/s, respectively. The two-tailed Student's t-test showed that the intestinal permeability of CsA was significantly increased by Ery in all four CsA concentrations used (P < 0.05). However, there was no significant difference between the Peff values of CsA in different concentrations, indicating that the CsA permeation was independent of the concentration. Therefore it is concluded that at least some part of the observed clinical interaction between Ery and CsA is due to the interaction in absorption level.

Are computational models of any use to psychiatry?

PubMed

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

2011-08-01

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

Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays.

PubMed

Harris, Kate; Aylott, Mike; Cui, Yi; Louttit, James B; McMahon, Nicholas C; Sridhar, Arun

2013-08-01

Human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are a potential source to develop assays for predictive electrophysiological safety screening. Published studies show that the relevant physiology and pharmacology exist but does not show the translation between stem cell cardiomyocyte assays and other preclinical safety screening assays, which is crucial for drug discovery and safety scientists and the regulators. Our studies are the first to show the pharmacology of ion channel blockade and compare them with existing functional cardiac electrophysiology studies. Ten compounds (a mixture of pure hERG [E-4031 and Cisapride], hERG and sodium [Flecainide, Mexiletine, Quinidine, and Terfenadine], calcium channel blockers [Nifedipine and Verapamil], and two proprietary compounds [GSK A and B]) were tested, and results from hiPSC-CMs studied on multielectrode arrays (MEA) were compared with other preclincial models and clinical drug concentrations and effects using integrated risk assessment plots. All ion channel blockers produced (1) functional effects on repolarization and depolarization around the IC25 and IC50 values and (2) excessive blockade of hERG and/or blockade of sodium current precipitated arrhythmias. Our MEA data show that hiPSC-CMs demonstrate relevant pharmacology and show excellent correlations to current functional cardiac electrophysiological studies. Based on these results, MEA assays using iPSC-CMs offer a reliable, cost effective, and surrogate to preclinical in vitro testing, in addition to the 3Rs (refine, reduce, and replace animals in research) benefit.

Test beam demonstration of silicon microstrip modules with transverse momentum discrimination for the future CMS tracking detector

NASA Astrophysics Data System (ADS)

Adam, W.; Bergauer, T.; Brondolin, E.; Dragicevic, M.; Friedl, M.; Frühwirth, R.; Hoch, M.; Hrubec, J.; König, A.; Steininger, H.; Treberspurg, W.; Waltenberger, W.; Alderweireldt, S.; Beaumont, W.; Janssen, X.; Lauwers, J.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Beghin, D.; 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.; Postiau, N.; Randle-Conde, A.; Seva, T.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Wang, Q.; Yang, Y.; Zenoni, F.; Zhang, F.; Abu Zeid, S.; Blekman, F.; De Bruyn, I.; De Clercq, J.; D'Hondt, J.; Deroover, K.; Lowette, S.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Van Mulders, P.; Van Parijs, I.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; Delaere, C.; Delcourt, M.; De Visscher, S.; Francois, B.; Giammanco, A.; Jafari, A.; Cabrera Jamoulle, J.; De Favereau De Jeneret, J.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Michotte, D.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Szilasi, N.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Härkönen, J.; Lampén, T.; Luukka, P.; Peltola, T.; Tuominen, E.; Tuovinen, E.; Eerola, P.; Baulieu, G.; Boudoul, G.; Caponetto, L.; Combaret, C.; Contardo, D.; Dupasquier, T.; Gallbit, G.; Lumb, N.; Mirabito, L.; Perries, S.; Vander Donckt, M.; Viret, S.; Agram, J.-L.; Andrea, J.; Bloch, D.; Bonnin, C.; Brom, J.-M.; Chabert, E.; Chanon, N.; Charles, L.; Conte, E.; Fontaine, J.-Ch.; Gross, L.; Hosselet, J.; Jansova, M.; Tromson, D.; Autermann, C.; Feld, L.; Karpinski, W.; Kiesel, K. M.; Klein, K.; Lipinski, M.; Ostapchuk, A.; Pierschel, G.; Preuten, M.; Rauch, M.; Schael, S.; Schomakers, C.; Schulz, J.; Schwering, G.; Wlochal, M.; Zhukov, V.; Pistone, C.; Fluegge, G.; Kuensken, A.; Pooth, O.; Stahl, A.; Aldaya, M.; Asawatangtrakuldee, C.; Beernaert, K.; Bertsche, D.; Contreras-Campana, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Gallo, E.; Garay Garcia, J.; Hansen, K.; Haranko, M.; Harb, A.; Hauk, J.; Keaveney, J.; Kalogeropoulos, A.; Kleinwort, C.; Lohmann, W.; Mankel, R.; Maser, H.; Mittag, G.; Muhl, C.; Mussgiller, A.; Pitzl, D.; Reichelt, O.; Savitskyi, M.; Schuetze, P.; Walsh, R.; Zuber, A.; Biskop, H.; Buhmann, P.; Centis-Vignali, M.; Garutti, E.; Haller, J.; Hoffmann, M.; Klanner, R.; Matysek, M.; Perieanu, A.; Scharf, Ch.; Schleper, P.; Schmidt, A.; Schwandt, J.; Sonneveld, J.; Steinbrück, G.; Vormwald, B.; Wellhausen, J.; Abbas, M.; Amstutz, C.; Barvich, T.; Barth, Ch.; Boegelspacher, F.; De Boer, W.; Butz, E.; Casele, M.; Colombo, F.; Dierlamm, A.; Freund, B.; Hartmann, F.; Heindl, S.; Husemann, U.; Kornmeyer, A.; Kudella, S.; Muller, Th.; Printz, M.; Simonis, H. J.; Steck, P.; Weber, M.; Weiler, Th.; Anagnostou, G.; Asenov, P.; Assiouras, P.; Daskalakis, G.; Kyriakis, A.; Loukas, D.; Paspalaki, L.; Siklér, F.; Veszprémi, V.; Bhardwaj, A.; Dalal, R.; Jain, G.; Ranjan, K.; Dutta, S.; Chowdhury, S. Roy; Bakhshiansohl, H.; Behnamian, H.; Khakzad, M.; Naseri, M.; Cariola, P.; Creanza, D.; De Palma, M.; De Robertis, G.; Fiore, L.; Franco, M.; Loddo, F.; Sala, G.; Silvestris, L.; Maggi, G.; My, S.; Selvaggi, G.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Saizu, M. A.; Tricomi, A.; Tuve, C.; Barbagli, G.; Brianzi, M.; Ciaranfi, R.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Latino, G.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Scarlini, E.; Sguazzoni, G.; Strom, D.; Viliani, L.; Ferro, F.; Lo Vetere, M.; Robutti, E.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Pedrini, D.; Azzi, P.; Bacchetta, N.; Bisello, D.; Dall'Osso, M.; Pozzobon, N.; Tosi, M.; De Canio, F.; Gaioni, L.; Manghisoni, M.; Nodari, B.; Riceputi, E.; Re, V.; Traversi, G.; Comotti, D.; Ratti, L.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Checcucci, B.; Ciangottini, D.; Fanò, L.; Gentsos, C.; Ionica, M.; Leonardi, R.; Manoni, E.; Mantovani, G.; Marconi, S.; Mariani, V.; Menichelli, M.; Modak, A.; Morozzi, A.; Moscatelli, F.; Passeri, D.; Placidi, P.; Postolache, V.; Rossi, A.; Saha, A.; Santocchia, A.; Storchi, L.; Spiga, D.; Androsov, K.; Azzurri, P.; Arezzini, S.; Bagliesi, G.; Basti, A.; Boccali, T.; Borrello, L.; Bosi, F.; Castaldi, R.; Ciampa, A.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Magazzu, G.; Martini, L.; Mazzoni, E.; Messineo, A.; Moggi, A.; Morsani, F.; Palla, F.; Palmonari, F.; Raffaelli, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Bellan, R.; Costa, M.; Covarelli, R.; Da Rocha Rolo, M.; Demaria, N.; Rivetti, A.; Dellacasa, G.; Mazza, G.; Migliore, E.; Monteil, E.; Pacher, L.; Ravera, F.; Solano, A.; Fernandez, M.; Gomez, G.; Jaramillo Echeverria, R.; Moya, D.; Gonzalez Sanchez, F. J.; Vila, I.; Virto, A. L.; Abbaneo, D.; Ahmed, I.; Albert, E.; Auzinger, G.; Berruti, G.; Bianchi, G.; Blanchot, G.; Bonnaud, J.; Caratelli, A.; Ceresa, D.; Christiansen, J.; Cichy, K.; Daguin, J.; D'Auria, A.; Detraz, S.; Deyrail, D.; Dondelewski, O.; Faccio, F.; Frank, N.; Gadek, T.; Gill, K.; Honma, A.; Hugo, G.; Jara Casas, L. M.; Kaplon, J.; Kornmayer, A.; Kottelat, L.; Kovacs, M.; Krammer, M.; Lenoir, P.; Mannelli, M.; Marchioro, A.; Marconi, S.; Mersi, S.; Martina, S.; Michelis, S.; Moll, M.; Onnela, A.; Orfanelli, S.; Pavis, S.; Peisert, A.; Pernot, J.-F.; Petagna, P.; Petrucciani, G.; Postema, H.; Rose, P.; Tropea, P.; Troska, J.; Tsirou, A.; Vasey, F.; Vichoudis, P.; Verlaat, B.; Zwalinski, L.; Bachmair, F.; Becker, R.; di Calafiori, D.; Casal, B.; Berger, P.; Djambazov, L.; Donega, M.; Grab, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lustermann, W.; Mangano, B.; Marionneau, M.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meinhard, M.; Perozzi, L.; Roeser, U.; Starodumov, A.; Tavolaro, V.; Wallny, R.; Zhu, D.; Amsler, C.; Bösiger, K.; Caminada, L.; Canelli, F.; Chiochia, V.; de Cosa, A.; Galloni, C.; Hreus, T.; Kilminster, B.; Lange, C.; Maier, R.; Ngadiuba, J.; Pinna, D.; Robmann, P.; Taroni, S.; Yang, Y.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Kaestli, H.-C.; Kotlinski, D.; Langenegger, U.; Meier, B.; Rohe, T.; Streuli, S.; Chen, P.-H.; Dietz, C.; Grundler, U.; Hou, W.-S.; Lu, R.-S.; Moya, M.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Jacob, J.; Seif El Nasr-Storey, S.; Cole, J.; Hoad, C.; Hobson, P.; Morton, A.; Reid, I. D.; Auzinger, G.; Bainbridge, R.; Dauncey, P.; Fulcher, J.; Hall, G.; James, T.; Magnan, A.-M.; Pesaresi, M.; Raymond, D. M.; Uchida, K.; Braga, D.; Coughlan, J. A.; Harder, K.; Jones, L.; Ilic, J.; Murray, P.; Prydderch, M.; Tomalin, I. R.; Garabedian, A.; Heintz, U.; Narain, M.; Nelson, J.; Sagir, S.; Speer, T.; Swanson, J.; Tersegno, D.; Watson-Daniels, J.; Chertok, M.; Conway, J.; Conway, R.; Flores, C.; Lander, R.; Pellett, D.; Ricci-Tam, F.; Squires, M.; Thomson, J.; Yohay, R.; Burt, K.; Ellison, J.; Hanson, G.; Olmedo, M.; Si, W.; Yates, B. R.; Gerosa, R.; Sharma, V.; Vartak, A.; Yagil, A.; Zevi Della Porta, G.; Dutta, V.; Gouskos, L.; Incandela, J.; Kyre, S.; Mullin, S.; Qu, H.; White, D.; Dominguez, A.; Bartek, R.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Apresyan, A.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chramowicz, J.; Christian, D.; Cooper, W. E.; Deptuch, G.; Derylo, G.; Gingu, C.; Grünendahl, S.; Hasegawa, S.; Hoff, J.; Howell, J.; Hrycyk, M.; Jindariani, S.; Johnson, M.; Kahlid, F.; Lei, C. M.; Lipton, R.; Lopes De Sá, R.; Liu, T.; Los, S.; Matulik, M.; Merkel, P.; Nahn, S.; Prosser, A.; Rivera, R.; Schneider, B.; Sellberg, G.; Shenai, A.; Spiegel, L.; Tran, N.; Uplegger, L.; Voirin, E.; Berry, D. R.; Chen, X.; Ennesser, L.; Evdokimov, A.; Evdokimov, O.; Gerber, C. E.; Hofman, D. J.; Makauda, S.; Mills, C.; Sandoval Gonzalez, I. D.; Alimena, J.; Antonelli, L. J.; Francis, B.; Hart, A.; Hill, C. S.; Parashar, N.; Stupak, J.; Bortoletto, D.; Bubna, M.; Hinton, N.; Jones, M.; Miller, D. H.; Shi, X.; Tan, P.; Baringer, P.; Bean, A.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Wilson, G.; Ivanov, A.; Mendis, R.; Mitchell, T.; Skhirtladze, N.; Taylor, R.; Anderson, I.; Fehling, D.; Gritsan, A.; Maksimovic, P.; Martin, C.; Nash, K.; Osherson, M.; Swartz, M.; Xiao, M.; Acosta, J. G.; Cremaldi, L. M.; Oliveros, S.; Perera, L.; Summers, D.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Monroy, J.; Siado, J.; Hahn, K.; Sevova, S.; Sung, K.; Trovato, M.; Bartz, E.; Gershtein, Y.; Halkiadakis, E.; Kyriacou, S.; Lath, A.; Nash, K.; Osherson, M.; Schnetzer, S.; Stone, R.; Walker, M.; Malik, S.; Norberg, S.; Ramirez Vargas, J. E.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kharchilava, A.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; McDermott, K.; Mirman, N.; Rinkevicius, A.; Ryd, A.; Salvati, E.; Skinnari, L.; Soffi, L.; Tao, Z.; Thom, J.; Tucker, J.; Zientek, M.; Akgün, B.; Ecklund, K. M.; Kilpatrick, M.; Nussbaum, T.; Zabel, J.; Betchart, B.; Covarelli, R.; Demina, R.; Hindrichs, O.; Petrillo, G.; Eusebi, R.; Patel, R.; Perloff, A.; Ulmer, K. A.; Delannoy, A. G.; D'Angelo, P.; Johns, W.

2018-03-01

A new CMS Tracker is under development for operation at the High Luminosity LHC from 2026 onwards. It includes an outer tracker based on dedicated modules that will reconstruct short track segments, called stubs, using spatially coincident clusters in two closely spaced silicon sensor layers. These modules allow the rejection of low transverse momentum track hits and reduce the data volume before transmission to the first level trigger. The inclusion of tracking information in the trigger decision is essential to limit the first level trigger accept rate. A customized front-end readout chip, the CMS Binary Chip (CBC), containing stub finding logic has been designed for this purpose. A prototype module, equipped with the CBC chip, has been constructed and operated for the first time in a 4 GeemVem/emc positron beam at DESY. The behaviour of the stub finding was studied for different angles of beam incidence on a module, which allows an estimate of the sensitivity to transverse momentum within the future CMS detector. A sharp transverse momentum threshold around 2 emVem/emc was demonstrated, which meets the requirement to reject a large fraction of low momentum tracks present in the LHC environment on-detector. This is the first realistic demonstration of a silicon tracking module that is able to select data, based on the particle's transverse momentum, for use in a first level trigger at the LHC . The results from this test are described here.

Explaining a CMS e e j j excess with R -parity violating supersymmetry and implications for neutrinoless double beta decay

NASA Astrophysics Data System (ADS)

Allanach, Ben; Biswas, Sanjoy; Mondal, Subhadeep; Mitra, Manimala

2015-01-01

A recent CMS search for the right-handed gauge boson WR reports an interesting deviation from the Standard Model. The search has been conducted in the e e j j channel and has shown a 2.8 σ excess around me e j j˜2 TeV . In this work, we explain the reported CMS excess with R -parity violating supersymmetry. We consider resonant selectron and sneutrino production, followed by the three body decays of the neutralino and chargino via an R -parity violating coupling. We fit the excess for slepton masses around 2 TeV. The scenario can further be tested in neutrinoless double beta decay (0 ν β β ) experiments. GERDA Phase-II will probe a significant portion of the good-fit parameter space.

A Conflict Management Scale for Pharmacy

PubMed Central

Gregory, Paul A.; Martin, Craig

2009-01-01

Objectives To develop and establish the validity and reliability of a conflict management scale specific to pharmacy practice and education. Methods A multistage inventory-item development process was undertaken involving 93 pharmacists and using a previously described explanatory model for conflict in pharmacy practice. A 19-item inventory was developed, field tested, and validated. Results The conflict management scale (CMS) demonstrated an acceptable degree of reliability and validity for use in educational or practice settings to promote self-reflection and self-awareness regarding individuals' conflict management styles. Conclusions The CMS provides a unique, pharmacy-specific method for individuals to determine and reflect upon their own conflict management styles. As part of an educational program to facilitate self-reflection and heighten self-awareness, the CMS may be a useful tool to promote discussions related to an important part of pharmacy practice. PMID:19960081

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...

A possible layout of the Spin Physics Detector with toroid magnet.

NASA Astrophysics Data System (ADS)

Nagaytsev, A. P.

2017-12-01

The Spin Physics Detector project for carrying out experiments at the 2-nd interaction point of the NICA collider is under preparation. The design of the collider allows reaching collision energy in the c.m.s. as high as √s = 26 GeV for polarized proton-proton collisions and √s = 12 GeV for polarized deuteron-deuteron collisons with a luminosity of up to 1032 cm2 s-1 (for protons) and 1031cm2s-1 for deuterons. Such a high luminosity of polarized beams interactions opens unique possibilities to investigate a variety of polarization phenomena including those related to the nucleon spin structure. A proposal for the experimental set-up based on a toroid type magnet is presented.

76 FR 56712 - CLIA Program and HIPAA Privacy Rule; Patients' Access to Test Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

...; Patients' Access to Test Reports AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS; Centers for...) regulations to specify that, upon a patient's request, the laboratory may provide access to completed test... provide for release of test reports to authorized persons and, if applicable, the individuals (or their...

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.

Dantrolene mediates vasorelaxation in cerebral vasoconstriction - A Case Series

PubMed Central

Muehlschlegel, Susanne; Rordorf, Guy; Bodock, Michael; Sims, John R.

2009-01-01

INTRODUCTION Cerebral vasoconstriction syndromes such as vasospasm after subarachnoid hemorrhage (SAH) and trauma, or Call-Fleming-Syndrome are difficult to treat, and can lead to substantial disability and death. Dantrolene, a ryanodine receptor antagonist, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We examined the effect of dantrolene on middle cerebral artery (MCA) blood flow velocities as measured by transcranial Doppler (TCD). METHODS Three consecutive patients with elevated MCA TCD velocities receiving dantrolene (2.5mg/kg IV q6h) were retrospectively reviewed. Average MCA peak systolic, mean flow velocities, and the pulsatility index (PI) before and after the dantrolene infusion were compared within patients. Systemic physiological parameters (blood pressure, heart rate, central venous pressure, intracranial pressure, body temperature and cooling water temperature) were recorded during 6 hours before and after the dantrolene infusion. RESULTS MCA peak systolic velocities (mean ± SE) for the three patients were 297 ± 3 cm/s, 248 ± 8 cm/s, and 268 ± 19 cm/s before dantrolene and 159 ± 9 cm/s, 169 ± 8 cm/s and 216 ± 12 cm/s after dantrolene. Average mean flow velocities showed the same trend. Interestingly, the PI increased slightly from 0.6, 0.52 and 0.67 before dantrolene, to 1.17, 0.71 and 0.77 after dantrolene. Systemic physiological parameters remained stable in all three patients. CONCLUSION Dantrolene attenuated cerebral vasoconstriction as measured by TCD without altering systemic physiological parameters. This suggests that intracellular calcium release from ryanodine channels in smooth muscle might play a role in vasospasm. A prospective study is underway to test this hypothesis. PMID:18696267

The pixel tracking telescope at the Fermilab Test Beam Facility

DOE PAGES

Kwan, Simon; Lei, CM; Menasce, Dario; ...

2016-03-01

An all silicon pixel telescope has been assembled and used at the Fermilab Test Beam Facility (FTBF) since 2009 to provide precise tracking information for different test beam experiments with a wide range of Detectors Under Test (DUTs) requiring high resolution measurement of the track impact point. The telescope is based on CMS pixel modules left over from the CMS forward pixel production. Eight planes are arranged to achieve a resolution of less than 8 μm on the 120 GeV proton beam transverse coordinate at the DUT position. In order to achieve such resolution with 100 × 150 μm 2more » pixel cells, the planes were tilted to 25 degrees to maximize charge sharing between pixels. Crucial for obtaining this performance is the alignment software, called Monicelli, specifically designed and optimized for this system. This paper will describe the telescope hardware, the data acquisition system and the alignment software constituting this particle tracking system for test beam users.« less

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

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

Liu, Paul

2012-05-01

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

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

PubMed Central

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

2014-01-01

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

Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro.

PubMed

Qian, Li; Berry, Emily C; Fu, Ji-dong; Ieda, Masaki; Srivastava, Deepak

2013-06-01

Cardiac fibroblasts can be reprogrammed to cardiomyocyte-like cells by the introduction of three transcription factors: Gata4, Mef2c and Tbx5 (collectively referred to here as GMT). Resident cardiac fibroblasts can be converted in vivo into induced cardiomyocyte-like cells (iCMs) that closely resemble endogenous cardiomyocytes and electrically integrate with the host myocardium. In contrast, in vitro reprogramming yields many partially reprogrammed iCMs, with a few that reprogram fully into contracting myocytes (~3 out of 10,000 GMT-transduced cells). iCMs can be observed as early as 3 d after viral infection, and they continue to mature over 2 months before beating is observed. Despite the success of multiple groups, the inefficiency of in vitro reprogramming has made it challenging for others. However, given the advantages of in vitro iCMs for performing mechanistic studies and, if refined, for testing drugs or small molecules for personalized medicine and modeling cardiac disease in a dish, it is important to standardize the protocol to improve reproducibility and enhance the technology further. Here we describe a detailed step-by-step protocol for in vitro cardiac reprogramming using retroviruses encoding GMT.

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

PubMed

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

2014-07-21

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

The CMS Tier0 goes cloud and grid for LHC Run 2

DOE PAGES

Hufnagel, Dirk

2015-12-23

In 2015, CMS will embark on a new era of collecting LHC collisions at unprecedented rates and complexity. This will put a tremendous stress on our computing systems. Prompt Processing of the raw data by the Tier-0 infrastructure will no longer be constrained to CERN alone due to the significantly increased resource requirements. In LHC Run 2, we will need to operate it as a distributed system utilizing both the CERN Cloud-based Agile Infrastructure and a significant fraction of the CMS Tier-1 Grid resources. In another big change for LHC Run 2, we will process all data using the multi-threadedmore » framework to deal with the increased event complexity and to ensure efficient use of the resources. Furthermore, this contribution will cover the evolution of the Tier-0 infrastructure and present scale testing results and experiences from the first data taking in 2015.« less

The CMS TierO goes Cloud and Grid for LHC Run 2

NASA Astrophysics Data System (ADS)

Hufnagel, Dirk

2015-12-01

In 2015, CMS will embark on a new era of collecting LHC collisions at unprecedented rates and complexity. This will put a tremendous stress on our computing systems. Prompt Processing of the raw data by the Tier-0 infrastructure will no longer be constrained to CERN alone due to the significantly increased resource requirements. In LHC Run 2, we will need to operate it as a distributed system utilizing both the CERN Cloud-based Agile Infrastructure and a significant fraction of the CMS Tier-1 Grid resources. In another big change for LHC Run 2, we will process all data using the multi-threaded framework to deal with the increased event complexity and to ensure efficient use of the resources. This contribution will cover the evolution of the Tier-0 infrastructure and present scale testing results and experiences from the first data taking in 2015.

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.

Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice

PubMed Central

Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E.; Qiang, Sheng

2015-01-01

Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China. PMID:26012494

Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice.

PubMed

Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E; Qiang, Sheng

2015-05-27

Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China.

Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression.

PubMed

Dang, Haixia; Chen, Ying; Liu, Xinmin; Wang, Qiong; Wang, Liwei; Jia, William; Wang, Yuqing

2009-11-13

Ginseng total saponins (GTS) are the major active components of Panax ginseng C.A. Meyer, which has been used as a popular tonic herb for 2000 years in Far East countries. In the present study, two classic animal models: the forced swimming test (FST) and the chronic mild stress (CMS) model were used to evaluate the antidepressant-like activities of GTS. It was observed that GTS at doses of 50 and 100 mg/kg significantly reduced the immobility time in the FST in mice after 7-day treatment. GTS also reversed the reduction in the sucrose preference index, decrease in locomotor activity as well as prolongation of latency of feeding in the novelty environment displayed by CMS rats. In addition, HPLC-ECD and immunohistochemical staining analysis indicated that the CMS-induced decrease in monoamine neurotransmitter concentration and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were almost completely reversed by GTS. In conclusion, GTS exerts antidepressant-like effects in two highly specific and predictive animal models of depression. The activity of GTS in antidepression may be mediated partly through enhancing the monoamine neurotransmitter concentration and BDNF expression in the hippocampus.

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

Heart deformation analysis for automated quantification of cardiac function and regional myocardial motion patterns: A proof of concept study in patients with cardiomyopathy and healthy subjects.

PubMed

Lin, Kai; Collins, Jeremy D; Chowdhary, Varun; Markl, Michael; Carr, James C

2016-10-01

To test the performance of HDA in characterizing left ventricular (LV) function and regional myocardial motion patterns in the context of cardiomyopathy based on cine cardiovascular magnetic resonance (CMR). Following the approval of the institutional review board (IRB), standard cine images of 45 subjects, including 15 healthy volunteers, 15 patients with hypertrophic cardiomyopathy (HCM) and 15 patients with dilated cardiomyopathy (DCM) were retrospectively analyzed using HDA. The variations of LV ejection fraction (LVEF), LV mass (LVM), and regional myocardial motion indices, including radial (Drr), circumferential (Dcc) displacement, radial (Vrr) and circumferential (Vcc) velocity, radial (Err), circumferential (Ecc) and shear (Ess) strain and radial (SRr) and circumferential (SRc) strain rate, were calculated and compared among subject groups. Inter-study reproducibility of HDA-derived myocardial motion indices were tested on 15 volunteers by using intra-class correlation coefficient (ICC) and coefficient of variation (CoV). HDA identified significant differences in cardiac function and motion indices between subject groups. DCM patients had significantly lower LVEF (33.5±9.65%), LVM (105.88±21.93g), peak Drr (0.29±0.11cm), Vrr-sys (2.14±0.72cm/s), Err (0.17±0.08), Ecc (-0.08±0.03), SRr-sys (0.91±0.44s(-1)) and SRc-sys (-0.64±0.27s(-1)) compared to the other two groups. HCM patients demonstrated increased LVM (171.69±34.19) and lower peak Vcc-dia (0.78±0.30cm/s) than other subjects. Good inter-study reproducibility was found for all HDA-derived myocardial indices in healthy volunteers (ICC=0.664-0.942, CoV=15.1%-37.1%). Without the need for operator interaction, HDA is a reproducible method for the automated characterization of global and regional LV function in the context of cardiomyopathy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

NoSQL technologies for the CMS Conditions Database

NASA Astrophysics Data System (ADS)

Sipos, Roland

2015-12-01

With the restart of the LHC in 2015, the growth of the CMS Conditions dataset will continue, therefore the need of consistent and highly available access to the Conditions makes a great cause to revisit different aspects of the current data storage solutions. We present a study of alternative data storage backends for the Conditions Databases, by evaluating some of the most popular NoSQL databases to support a key-value representation of the CMS Conditions. The definition of the database infrastructure is based on the need of storing the conditions as BLOBs. Because of this, each condition can reach the size that may require special treatment (splitting) in these NoSQL databases. As big binary objects may be problematic in several database systems, and also to give an accurate baseline, a testing framework extension was implemented to measure the characteristics of the handling of arbitrary binary data in these databases. Based on the evaluation, prototypes of a document store, using a column-oriented and plain key-value store, are deployed. An adaption layer to access the backends in the CMS Offline software was developed to provide transparent support for these NoSQL databases in the CMS context. Additional data modelling approaches and considerations in the software layer, deployment and automatization of the databases are also covered in the research. In this paper we present the results of the evaluation as well as a performance comparison of the prototypes studied.

The utility of rat jejunal permeability for biopharmaceutics classification system.

PubMed

Zakeri-Milani, Parvin; Valizadeh, Hadi; Tajerzadeh, Hosnieh; Islambulchilar, Ziba

2009-12-01

The biopharmaceutical classification system has been developed to provide a scientific approach for classifying drug compounds based on their dose/solubility ratio and human intestinal permeability. Therefore in this study a new classification is presented, which is based on a correlation between rat and human intestinal permeability values. In situ technique in rat jejunum was used to determine the effective intestinal permeability of tested drugs. Then three dimensionless parameters--dose number, absorption number, and dissolution number (D(o), A(n), and D(n))--were calculated for each drug. Four classes of drugs were defined, that is, class I, D(0) < 0.5, P(eff(rat)) > 5.09 x 10(-5) cm/s; class II, D(o) > 1, P(eff(rat)) > 5.09 x 10( -5) cm/s; class III, D(0) < 0.5, P(eff(rat)) < 4.2 x 10(-5) cm/s; and class IV, D(o) > 1, P(eff(rat)) < 4.2 x 10(-5) cm/s. A region of borderline drugs (0.5 < D(o) < 1, 4.2 x 10(-5) < P(eff(rat)) < 5.09 x 10(-5) cm/s) was also defined. According to obtained results and proposed classification for drugs, it is concluded that drugs could be categorized correctly based on dose number and their intestinal permeability values in rat model using single-pass intestinal perfusion technique. This classification enables us to remark defined characteristics for intestinal absorption of all four classes using suitable cutoff points for both dose number and rat effective intestinal permeability values.

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

PubMed Central

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

2012-01-01

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

Downscaling Global Emissions and Its Implications Derived from Climate Model Experiments

PubMed Central

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

2017-01-01

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

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

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.

Impact of the 2013 National Rollout of CMS Competitive Bidding Program: The Disruption Continues.

PubMed

Puckrein, Gary A; Hirsch, Irl B; Parkin, Christopher G; Taylor, Bruce T; Xu, Liou; Marrero, David G

2018-05-01

Use of glucose monitoring is essential to the safety of individuals with insulin-treated diabetes. In 2011, the Centers for Medicare & Medicaid Services (CMS) implemented the Medicare Competitive Bidding Program (CBP) in nine test markets. This resulted in a substantial disruption of beneficiary access to self-monitoring of blood glucose (SMBG) supplies and significant increases in the percentage of beneficiaries with either reduced or no acquisition of supplies. These reductions were significantly associated with increased mortality, hospitalizations, and costs. The CBP was implemented nationally in July 2013. We evaluated the impact of this rollout to determine if the adverse outcomes seen in 2011 persisted. This longitudinal study followed 529,627 insulin-treated beneficiaries from 2009 through 2013 to assess changes in beneficiary acquisition of testing supplies in the initial nine test markets (TEST, n = 43,939) and beneficiaries not affected by the 2011 rollout (NONTEST, n = 485,688). All Medicare beneficiary records for analysis were obtained from CMS. The percentages of beneficiaries with partial/no SMBG acquisition were significantly higher in both the TEST (37.4%) and NONTEST (37.6%) groups after the first 6 months of the national CBP rollout, showing increases of 48.1% and 60.0%, respectively (both P < 0.0001). The percentage of beneficiaries with no record for SMBG acquisition increased from 54.1% in January 2013 to 62.5% by December 2013. Disruption of beneficiary access to their prescribed SMBG supplies has persisted and worsened. Diabetes testing supplies should be excluded from the CBP until transparent, science-based methodologies for safety monitoring are adopted and implemented. © 2017 by the American Diabetes Association.

The High Luminosity LHC Project

NASA Astrophysics Data System (ADS)

Rossi, Lucio

The High Luminosity LHC is one of the major scientific project of the next decade. It aims at increasing the luminosity reach of LHC by a factor five for peak luminosity and a factor ten in integrated luminosity. The project, now fully approved and funded, will be finished in ten years and will prolong the life of LHC until 2035-2040. It implies deep modifications of the LHC for about 1.2 km around the high luminosity insertions of ATLAS and CMS and relies on new cutting edge technologies. We are developing new advanced superconducting magnets capable of reaching 12 T field; superconducting RF crab cavities capable to rotate the beams with great accuracy; 100 kA and hundred meter long superconducting links for removing the power converter out of the tunnel; new collimator concepts, etc... Beside the important physics goals, the High Luminosity LHC project is an ideal test bed for new technologies for the next hadron collider for the post-LHC era.

New experimental constrains on chiral magnetic effect using charge-dependent azimuthal correlation in pPb and PbPb collisions at the LHC

NASA Astrophysics Data System (ADS)

Tu, Zhoudunming

2018-01-01

Studies of charge-dependent azimuthal correlations for the same- and oppositesign particle pairs are presented in PbPb collisions at 5 TeV and pPb collisions at 5 and 8.16 TeV, with the CMS experiment at the LHC. The azimuthal correlations are evaluated with respect to the second- and also higher-order event planes, as a function of particle pseudorapidity and transverse momentum, and event multiplicity. By employing an event-shape engineering technique, the dependence of correlations on azimuthal anisotropy flow is investigated. Results presented provide new insights to the origin of observed charge-dependent azimuthal correlations, and have important implications to the search for the chiral magnetic effect in heavy ion collisions.

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...

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.

Large-scale natural gradient tracer test in sand and gravel, Cape Cod, Massachusetts: 3. Hydraulic conductivity variability and calculated macrodispersivities

USGS Publications Warehouse

Hess, Kathryn M.; Wolf, Steven H.; Celia, Michael A.

1992-01-01

Hydraulic conductivity (K) variability in a sand and gravel aquifer on Cape Cod, Massachusetts, was measured and subsequently used in stochastic transport theories to estimate macrodispersivities. Nearly 1500 K measurements were obtained by borehole flowmeter tests and permeameter analyses of cores. The geometric mean for the flowmeter tests (0.11 cm/s) is similar to that estimated from other field tests. The mean for the permeameter tests (0.035 cm/s) is significantly lower, possibly because of compaction of the cores. The variance for the flowmeter (0.24) is also greater than that for the permeameter (0.14). Geostatistical analyses applying negative exponential models with and without nuggets reveal similar spatial correlation structures for the two data sets. Estimated correlation scales range from 2.9 to 8 m in the horizontal and from 0.18 to 0.38 m in the vertical. Estimates of asymptotic longitudinal dispersivity (b.35–0.78 m) are similar in magnitude to that observed in the natural gradient tracer test (0.96 m) previously conducted at this site.

Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

PubMed

Odening, Katja E; Jung, Bernd A; Lang, Corinna N; Cabrera Lozoya, Rocio; Ziupa, David; Menza, Marius; Relan, Jatin; Franke, Gerlind; Perez Feliz, Stefanie; Koren, Gideon; Zehender, Manfred; Bode, Christoph; Brunner, Michael; Sermesant, Maxime; Föll, Daniela

2013-10-01

Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder. © 2013 Heart Rhythm Society. All rights reserved.

Conceptual design of the cryostat for the new high luminosity (HL-LHC) triplet magnets

NASA Astrophysics Data System (ADS)

Ramos, D.; Parma, V.; Moretti, M.; Eymin, C.; Todesco, E.; Van Weelderen, R.; Prin, H.; Berkowitz Zamora, D.

2017-12-01

The High Luminosity LHC (HL-LHC) is a project to upgrade the LHC collider after 2020-2025 to increase the integrated luminosity by about one order of magnitude and extend the physics production until 2035. An upgrade of the focusing triplets insertion system for the ATLAS and CMS experiments is foreseen using superconducting magnets operating in a pressurised superfluid helium bath at 1.9 K. This will require the design and construction of four continuous cryostats, each about sixty meters in length and one meter in diameter, for the final beam focusing quadrupoles, corrector magnets and beam separation dipoles. The design is constrained by the dimensions of the existing tunnel and accessibility restrictions imposing the integration of cryogenic piping inside the cryostat, thus resulting in a very compact integration. As the alignment and position stability of the magnets is crucial for the luminosity performance of the machine, the magnet support system must be carefully designed in order to cope with parasitic forces and thermo-mechanical load cycles. In this paper, we present the conceptual design of the cryostat and discuss the approach to address the stringent and often conflicting requirements of alignment, integration and thermal aspects.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

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.

Generation of Cardiomyocytes from Pluripotent Stem Cells.

PubMed

Nakahama, Hiroko; Di Pasquale, Elisa

2016-01-01

The advent of pluripotent stem cells (PSCs) enabled a multitude of studies for modeling the development of diseases and testing pharmaceutical therapeutic potential in vitro. These PSCs have been differentiated to multiple cell types to demonstrate its pluripotent potential, including cardiomyocytes (CMs). However, the efficiency and efficacy of differentiation vary greatly between different cell lines and methods. Here, we describe two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation.

QCD Physics with the CMS Experiment

NASA Astrophysics Data System (ADS)

Cerci, S.

2017-12-01

Jets which are the signatures of quarks and gluons in the detector can be described by Quantum Chromodynamics (QCD) in terms of parton-parton scattering. Jets are abundantly produced at the LHC's high energy scales. Measurements of inclusive jets, dijets and multijets can be used to test perturbative QCD predictions and to constrain parton distribution functions (PDF), as well as to measure the strong coupling constant αS . The measurements use the samples of proton-proton collisions collected with the CMS detector at the LHC at various center-of-mass energies of 7, 8 and 13 TeV.

Ada (Trade Name) Compiler Validation Summary Report: IBM Corporation. IBM Development System for the Ada Language System, Version 1.1.0, IBM 4381 under VM/SP CMS, Release 3.6.

DTIC Science & Technology

1988-05-19

System for the Ada Language System, Version 1.1.0, 1.% International Business Machines Corporation, Wright-Patterson AFB. IBM 4381 under VM/SP CMS...THIS PAGE (When Data Enre’ed) AVF Control Number: AVF-VSR-82.1087 87-03-10-TEL ! Ada® COMPILER VALIDATION SUMMARY REPORT: International Business Machines...Organization (AVO). On-site testing was conducted from !8 May 1987 through 19 May 1987 at International Business Machines -orporation, San Diego CA. 1.2

Ada (Trade Name) Compiler Validation Summary Report: International Business Machines Corporation. IBM Development System for the Ada Language System, Version 1.1.0, IBM 4381 under VM/SP CMS Host, IBM 4381 under MVS Target

DTIC Science & Technology

1988-05-20

AVF Control Number: AVF-VSR-84.1087 ’S (0 87-03-10-TEL I- Ada® COMPILER VALIDATION SUMMARY REPORT: International Business Machines Corporation IBM...System, Version 1.1.0, International Business Machines Corporation, Wright-Patterson AFB. IBM 4381 under VM/SP CMS, Release 3.6 (host) and IBM 4381...an IBM 4381 operating under MVS, Release 3.8. On-site testing was performed 18 May 1987 through 20 May 1987 at International Business Machines

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.

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

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.

SiPM based readout system for PbWO4 crystals

NASA Astrophysics Data System (ADS)

Berra, A.; Bolognini, D.; Bonfanti, S.; Bonvicini, V.; Lietti, D.; Penzo, A.; Prest, M.; Stoppani, L.; Vallazza, E.

2013-08-01

Silicon PhotoMultipliers (SiPMs) consist of a matrix of small passively quenched silicon avalanche photodiodes operated in limited Geiger-mode (GM-APDs) and read out in parallel from a common output node. Each pixel (with a typical size in the 20-100 μm range) gives the same current response when hit by a photon; the SiPM output signal is the sum of the signals of all the pixels, which depends on the light intensity. The main advantages of SiPMs with respect to photomultiplier tubes (PMTs) are essentially the small dimensions, the insensitivity to magnetic fields and a low bias voltage. This contribution presents the performance of a SiPM based readout system for crystal calorimeters developed in the framework of the FACTOR/TWICE collaboration. The SiPM used for the test is a new device produced by FBK-irst which consists in a matrix of four sensors embedded in the same silicon substrate, called QUAD. The SiPM has been coupled to a lead tungstate crystal, an early-prototype version of the crystals developed for the electromagnetic calorimeter of the CMS experiment. New tests are foreseen using a complete module consisting of nine crystals, each one readout by two QUADs.

Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Chaudhari, Umesh; Nemade, Harshal; Sureshkumar, Poornima; Vinken, Mathieu; Ates, Gamze; Rogiers, Vera; Hescheler, Jürgen; Hengstler, Jan Georg; Sachinidis, Agapios

2018-01-01

There is a large demand of a human relevant in vitro test system suitable for assessing the cardiotoxic potential of cosmetic ingredients and other chemicals. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we have already established an in vitro cardiotoxicity assay and identified genomic biomarkers of anthracycline-induced cardiotoxicity in our previous work. Here, five cosmetic ingredients were studied by the new hiPSC-CMs test; kojic acid (KJA), triclosan (TS), triclocarban (TCC), 2,7-naphthalenediol (NPT), and basic red 51 (BR51) based on cytotoxicity as well as ATP assays, beating rate, and genomic biomarkers to determine the lowest observed effect concentration (LOEC) and no observed effect concentration (NOEC). The LOEC for beating rate were 400, 10, 3, >400, and 3 µM for KJA, TS, TCC, NPT, and BR51, respectively. The corresponding concentrations for cytotoxicity or ATP depletion were similar, with the exception of TS and TCC, where the cardiomyocyte-beating assay showed positive results at non-cytotoxic concentrations. Functional analysis also showed that the individual compounds caused different effects on hiPSC-CMs. While exposure to KJA, TS, TCC, and BR51 induced significant arrhythmic beating, NPT slightly decreased cell viability, but did not influence beating. Gene expression studies showed that TS and NPT caused down-regulation of cytoskeletal and cardiac ion homeostasis genes. Moreover, TS and NPT deregulated genomic biomarkers known to be affected also by anthracyclines. The present study demonstrates that hiPSC-CMs can be used to determine LOECs and NOECs in vitro, which can be compared to human blood concentrations to determine margins of exposure. Our in vitro assay, which so far has been tested with several anthracyclines and cosmetics, still requires validation by larger numbers of positive and negative controls, before it can be recommended for routine analysis.

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.

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...

42 CFR 414.509 - Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) or § 414.509(a)(3) that the basis for payment for a new test will be gapfilling, CMS posts interim... for a new clinical diagnostic laboratory test. 414.509 Section 414.509 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests...

42 CFR 422.510 - Termination of contract by CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

The diverse use of clouds by CMS

DOE PAGES

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

2015-12-23

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

Automated digital magnetofluidics

NASA Astrophysics Data System (ADS)

Schneider, J.; Garcia, A. A.; Marquez, M.

2008-08-01

Drops can be moved in complex patterns on superhydrophobic surfaces using a reconfigured computer-controlled x-y metrology stage with a high degree of accuracy, flexibility, and reconfigurability. The stage employs a DMC-4030 controller which has a RISC-based, clock multiplying processor with DSP functions, accepting encoder inputs up to 22 MHz, provides servo update rates as high as 32 kHz, and processes commands at rates as fast as 40 milliseconds. A 6.35 mm diameter cylindrical NdFeB magnet is translated by the stage causing water drops to move by the action of induced magnetization of coated iron microspheres that remain in the drop and are attracted to the rare earth magnet through digital magnetofluidics. Water drops are easily moved in complex patterns in automated digital magnetofluidics at an average speed of 2.8 cm/s over a superhydrophobic polyethylene surface created by solvent casting. With additional components, some potential uses for this automated microfluidic system include characterization of superhydrophobic surfaces, water quality analysis, and medical diagnostics.

Plasma Clouds and Snowplows: Bulk Plasma Escape from Mars Observed by MAVEN

NASA Technical Reports Server (NTRS)

Halekas, J. S.; Brain, D. A.; Ruhunusiri, S.; McFadden, J. P.; Mitchell, D. L.; Mazelle, C.; Connerney, J. E. P.; Harada, Y.; Hara, T.; Espley, J. R.;

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.

Novel laboratory simulations of astrophysical jets

NASA Astrophysics Data System (ADS)

Brady, Parrish Clawson

This thesis was motivated by the promise that some physical aspects of astrophysical jets and collimation processes can be scaled to laboratory parameters through hydrodynamic scaling laws. The simulation of astrophysical jet phenomena with laser-produced plasmas was attractive because the laser- target interaction can inject energetic, repeatable plasma into an external environment. Novel laboratory simulations of astrophysical jets involved constructing and using the YOGA laser, giving a 1064 nm, 8 ns pulse laser with energies up to 3.7 + 0.2 J . Laser-produced plasmas were characterized using Schlieren, interferometry and ICCD photography for their use in simulating jet and magnetosphere physics. The evolution of the laser-produced plasma in various conditions was compared with self-similar solutions and HYADES computer simulations. Millimeter-scale magnetized collimated outflows were produced by a centimeter scale cylindrically symmetric electrode configuration triggered by a laser-produced plasma. A cavity with a flared nozzle surrounded the center electrode and the electrode ablation created supersonic uncollimated flows. This flow became collimated when the center electrode changed from an anodeto a cathode. The plasma jets were in axially directed permanent magnetic fields with strengths up to 5000 Gauss. The collimated magnetized jets were 0.1-0. 3 cm wide, up to 2.0 cm long, and had velocities of ~4.0 × 10 6 cm/s. The dynamics of the evolution of the jet were compared qualitatively and quantitatively with fluxtube simulations from Bellan's formulation [6] giving a calculated estimate of ~2.6 × 10 6 cm/s for jet evolution velocity and evidence for jet rotation. The density measured with interferometry was 1.9 ± 0.2 × 10 17 cm -3 compared with 2.1 × 10 16 cm -3 calculated with Bellan's pressure balance formulation. Kinks in the jet column were produced consistent with the Kruskal-Shafranov condition which allowed stable and symmetric jets to form with the background magnetic fields. The Euler number for the laboratory jet was 9 compared with an estimate of 40 for young stellar object jets [135] which demonstrated adequate scaling between the two frames. A second experiment was performed concerning laboratory simulations of magnetospheres with plasma winds impinging on permanent magnetic dipoles. The ratio of the magnetopause measured with ICCD photography to the calculated magnetopause standoff distance was ~2.

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

CMS-Wave

DTIC Science & Technology

2015-10-30

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

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2016-12-01

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

CSAHi study-2: Validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes: Assessment of reference compounds and comparison with non-clinical studies and clinical information.

PubMed

Nozaki, Yumiko; Honda, Yayoi; Watanabe, Hitoshi; Saiki, Shota; Koyabu, Kiyotaka; Itoh, Tetsuji; Nagasawa, Chiho; Nakamori, Chiaki; Nakayama, Chiaki; Iwasaki, Hiroshi; Suzuki, Shinobu; Tanaka, Kohji; Takahashi, Etsushi; Miyamoto, Kaori; Morimura, Kaoru; Yamanishi, Atsuhiro; Endo, Hiroko; Shinozaki, Junko; Nogawa, Hisashi; Shinozawa, Tadahiro; Saito, Fumiyo; Kunimatsu, Takeshi

2017-08-01

With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period. The hiPS-CMs/MEA assay accurately predicted reference compounds potential for arrhythmogenesis, and yielded results that showed better correlation with target concentrations of QTc prolongation or TdP in clinical setting than other current in vitro and in vivo assays. Gene expression analyses revealed consistent profiles in all samples within and among the testing facilities. This report would provide CiPA with informative guidance on the use of the hiPS-CMs/MEA assay, and promote the establishment of a new paradigm, beyond conventional in vitro and in vivo assays for cardiac safety assessment of new drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-11-07

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

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

PubMed

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

2018-03-15

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

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

PubMed

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

2016-10-01

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

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

PubMed

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

2018-05-01

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

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

PubMed

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

2013-08-01

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

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

PubMed

Vaithianathan, Soundarya; Raman, Siddarth; Jiang, Wenlei; Ting, Tricia Y; Kane, Maureen A; Polli, James E

2015-07-06

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

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.

CMS Connect

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

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

PubMed

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

2013-02-01

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

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

PubMed

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

2011-11-01

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

76 FR 39110 - Medicare Program; Section 3113: The Treatment of Certain Complex Diagnostic Laboratory Tests...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... access to care, quality of care, health outcomes, and expenditures. DATES: Supporting information to... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-5058-N... Tests Demonstration. The Demonstration is mandated by section 3113 of the Affordable Care Act. This...

78 FR 32657 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-31

... initiatives using a mixture of qualitative and quantitative consumer research strategies (including formative research studies and methodological tests) to improve communication with key CMS audiences. As new... Testing Research; Use: The purpose of this submission is to request an Information Collection Request (ICR...

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...

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

Estudio de un microcable de par trenzado para la comunicacion y lectura del modulo de pixeles del experimento CMS

NASA Astrophysics Data System (ADS)

Oliveros Tautiva, Sandra Jimena

The Compact Muon Solenoid (CMS) is one of the two most important experiments at the Large Hadron Collider (LHC). The pixel detector is the component closest to the collision in CMS and it receives large doses of radiation which will affect its performance. The pixel detector will be replaced by a new one after four years. The aim is to reduce material in the sensitive zone of the new pixel detector, which leads to the implementation of a type of micro twisted pair cable that will replace the existing kapton cables and some connections will be eliminated. The purpose of this work was to study the viability of using these micro twisted pair cables in the existing 40 MHz analog readout. The electrical parameters of micro cables were determined, and operational tests were performed in a module using these cables for communicating and reading. Three different lengths of micro cables were used, 1.0, 1.5 and 2.0 m, in order to compare test results with those obtained using the kapton cable. It was found that the use of these cables does not affect the programming and reading of the pixels in one module, so the micro cables are viable to be used in place of the kapton cables.

Day and night: diurnal phase influences the response to chronic mild stress

PubMed Central

Aslani, Shilan; Harb, Mazen R.; Costa, Patricio S.; Almeida, Osborne F. X.; Sousa, Nuno; Palha, Joana A.

2014-01-01

Chronic mild stress (CMS) protocols are widely used to create animal models of depression. Despite this, the inconsistencies in the reported effects may be indicative of crucial differences in methodology. Here, we considered the time of the diurnal cycle in which stressors are applied as a possible relevant temporal variable underlying the association between stress and behavior. Most laboratories test behavior during the light phase of the diurnal cycle, which corresponds to the animal's resting period. Here, rats stressed either in their resting (light phase) or active (dark phase) periods were behaviorally characterized in the light phase. When exposure to CMS occurred during the light phase of the day cycle, rats displayed signs of depressive and anxiety-related behaviors. This phenotype was not observed when CMS was applied during the dark (active) period. Interestingly, although no differences in spatial and reference memory were detected (Morris water maze) in animals in either stress period, those stressed in the light phase showed marked impairments in the probe test. These animals also showed significant dendritic atrophy in the hippocampal dentate granule neurons, with a decrease in the number of spines. Taken together, the observations reported demonstrate that the time in which stress is applied has differential effects on behavioral and neurostructural phenotypes. PMID:24672446

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 .

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

PubMed

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

2014-04-30

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

Opportunistic Resource Usage in CMS

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

Performance of the Prototype Readout System for the CMS Endcap Hadron Calorimeter Upgrade

NASA Astrophysics Data System (ADS)

Chaverin, Nate; Dittmann, Jay; Hatakeyama, Kenichi; Pastika, Nathaniel; CMS Collaboration

2016-03-01

The Compact Muon Solenoid (CMS) experiment at the CERN Large Hadron Collider (LHC) will upgrade the photodetectors and readout systems of the endcap hadron calorimeter during the technical stop scheduled for late 2016 and early 2017. A major milestone for this project was a highly successful testbeam run at CERN in August 2015. The testbeam run served as a full integration test of the electronics, allowing a study of the response of the preproduction electronics to the true detector light profile, as well as a test of the light yield of various new plastic scintillator materials. We present implications for the performance of the hadron calorimeter front-end electronics based on testbeam data, and we report on the production status of various components of the system in preparation for the upgrade.

Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

PubMed

Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

2017-08-01

Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

42 CFR 414.509 - Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) or § 414.509(a)(3) that the basis for payment for a new test will be gapfilling, CMS posts interim... for a new clinical diagnostic laboratory test. 414.509 Section 414.509 Public Health CENTERS FOR... Laboratory Tests § 414.509 Reconsideration of basis for and amount of payment for a new clinical diagnostic...

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2009-02-01

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

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

PubMed Central

2011-01-01

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

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

PubMed

Kiss, Alexander; Majercikova, Zuzana

2017-02-01

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

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

PubMed

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

2012-06-01

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

Opportunistic Resource Usage in CMS

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

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

2014-01-01

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

42 CFR 423.890 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

45 CFR 150.221 - Transition to State enforcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

45 CFR 150.213 - Form and content of notice.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

45 CFR 150.343 - Notice of proposed penalty.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

78 FR 3899 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-17

... methodological tests) to improve communication with key CMS audiences. As new information resources and... referred to as the Social Marketing and Consumer Testing Item Bank. This item bank is designed to establish... telephone surveys. The other set is less structured and is designed for use in qualitative one-on-one and...

40 CFR 63.1210 - What are the notification requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

... change in information already provided under § 63.9. 63.1206(b)(5)(i) Notification of changes in design...), 63.9(e) 63.9(g)(1) and (3) Notification of performance test and continuous monitoring system evaluation, including the performance test plan and CMS performance evaluation plan.1 63.1210(b) Notification...

40 CFR 63.1210 - What are the notification requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

... change in information already provided under § 63.9. 63.1206(b)(5)(i) Notification of changes in design...), 63.9(e) 63.9(g)(1) and (3) Notification of performance test and continuous monitoring system evaluation, including the performance test plan and CMS performance evaluation plan.1 63.1210(b) Notification...

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

PubMed

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

2018-02-23

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

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

PubMed

Liu, Longjian; Núñez, Ana E

2010-07-01

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

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

PubMed

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

2010-06-24

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

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

PubMed

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

2017-05-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-14

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

Enabling opportunistic resources for CMS Computing Operations

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

Hufnagel, Dirk

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

Enabling opportunistic resources for CMS Computing Operations

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

Hufnagel, Dick

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

Enabling opportunistic resources for CMS Computing Operations

DOE PAGES

Hufnagel, Dirk

2015-12-23

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

ω-3 and folic acid act against depressive-like behavior and oxidative damage in the brain of rats subjected to early- or late-life stress.

PubMed

Réus, Gislaine Z; Maciel, Amanda L; Abelaira, Helena M; de Moura, Airam B; de Souza, Thays G; Dos Santos, Thais R; Darabas, Ana Caroline; Parzianello, Murilo; Matos, Danyela; Abatti, Mariane; Vieira, Ana Carolina; Fucillini, Vanessa; Michels, Monique; Dal-Pizzol, Felipe; Quevedo, João

2018-03-30

To investigate the antidepressant and antioxidant effects of omega-3, folic acid and n-acetylcysteine (NAC) in rats which were subjected to early or late life stress. Early stress was induced through maternal deprivation (MD), while late life stress was induced using the chronic mild stress (CMS) protocol. Young rats which were subjected to MD and the adult rats which were subjected to CMS were treated with omega-3 fatty acids (0.72 g/kg), NAC (20 mg/kg) or folic acid (50 mg/kg) once/day, for a period of 20 days. Then, the animals' immobility times were evaluated using the forced swimming test. Oxidative stress parameters were evaluated in the brain. Depressive-like behavior induced by CMS was prevented by NAC and folic acid, and depressive-like behavior induced by MD was prevented by NAC, folic acid and omega-3. NAC, folic acid and omega-3 were able to exert antioxidant effects in the brain of rats subjected to CMS or MD. These preventive treatments decreased the levels of protein carbonylation and lipid peroxidation, and also decreased the concentrations of nitrite/nitrate and reduced the activity of myeloperoxidase activity in the rat brain which was induced by CMS or MD. NAC, folic acid and omega-3 increased superoxide dismutase and catalase activities in the rat brain subjected to early or late life stress. NAC, omega-3 and folic acid may present interesting lines of treatment based on their antioxidant properties, which cause an inhibition of behavioral and brain changes that occur from stressful life events. Copyright © 2018 Elsevier Inc. All rights reserved.

Utilization of a clinical microbiology service at a Cambodian paediatric hospital and its impact on appropriate antimicrobial prescribing.

PubMed

Fox-Lewis, Shivani; Pol, Sreymom; Miliya, Thyl; Day, Nicholas P J; Turner, Paul; Turner, Claudia

2018-02-01

Antimicrobial resistance threatens human health worldwide. Antimicrobial misuse is a major driver of resistance. Promoting appropriate antimicrobial use requires an understanding of how clinical microbiology services are utilized, particularly in resource-limited settings. To assess the appropriateness of antimicrobial prescribing and the factors affecting utilization of the established clinical microbiology service (CMS). The CMS comprises the microbiology laboratory, clinical microbiologists (infection doctors) and antimicrobial treatment guidelines. This mixed-methods study was conducted at a non-governmental Cambodian paediatric hospital. Empirical and post-culture antimicrobial prescriptions were reviewed from medical records. The random sample included 10 outpatients per week in 2016 (retrospective) and 20 inpatients per week for 4 weeks in the medical, neonatal and intensive care wards (prospective). Post-culture prescriptions were assessed in patients with positive blood and cerebrospinal fluid cultures from 1 January 2014 to 31 December 2016. Focus group discussions and semi-structured interviews with clinicians explored barriers and facilitators to use of the CMS. Only 31% of outpatients were prescribed empirical antimicrobials. Post-culture prescriptions (394/443, 89%) were more likely to be appropriate than empirical prescriptions (447/535, 84%), based on treatment guidelines, microbiology advice and antimicrobial susceptibility test results (P = 0.015). Being comprehensive, accessible and trusted enabled CMS utilization. Clinical microbiologists provided a crucial human interface between the CMS and physicians. The main barriers were a strong clinical hierarchy and occasional communication difficulties. Antimicrobial prescribing in this hospital was largely appropriate. A culturally appropriate human interface linking the laboratory and physicians is essential in providing effective microbiology services and ensuring appropriate antimicrobial prescribing in resource-limited settings. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Calibration of echocardiographic tissue doppler velocity, using simple universally applicable methods

NASA Astrophysics Data System (ADS)

Dhutia, Niti M.; Zolgharni, Massoud; Willson, Keith; Cole, Graham; Nowbar, Alexandra N.; Manisty, Charlotte H.; Francis, Darrel P.

2014-03-01

Some of the challenges with tissue Doppler measurement include: apparent inconsistency between manufacturers, uncertainty over which part of the trace to make measurements and a lack of calibration of measurements. We develop and test tools to solve these problems in echocardiography laboratories. We designed and constructed an actuator and phantom setup to produce automatic reproducible motion, and used it to compare velocities measured using 3 echocardiographic modalities: M-mode, speckle tracking, and tissue Doppler, against a non-ultrasound, optical gold standard. In the clinical phase, 25 patients underwent M-mode, speckle tracking and tissue Doppler measurements of tissue velocities. In-vitro, the M-mode and speckle tracking velocities were concordant with optical assessment. Of the three possible tissue Doppler measurement conventions (outer, middle and inner line) only the middle line agreed with the optical assessment (discrepancy -0.20 (95% confidence interval -0.44 to 0.03)cm/s, p=0.11, outer +5.19(4.65 to 5.73)cm/s, p<0.0001, inner -6.26(-6.87 to -5.65)cm/s, p<0.0001). All 4 studied manufacturers showed a similar pattern. M-mode was therefore chosen as the in-vivo gold standard. Clinical measurements of tissue velocities by speckle tracking and the middle line of the tissue Doppler were concordant with M-mode, while the outer line significantly overestimated (+1.27(0.96 to 1.59)cm/s, p<0.0001) and the inner line underestimated (-1.81(-2.11 to -1.52)cm/s, p<0.0001). Echocardiographic velocity measurements can be calibrated by simple, inexpensive tools. We found that the middle of the tissue Doppler trace represents velocity correctly. Echocardiographers requiring velocities to match between different equipment, settings or modalities should use the middle line as the "guideline".

Human Embryonic Stem Cell-Derived Cardiomyocytes Migrate in Response to Gradients of Fibronectin and Wnt5a

PubMed Central

Moyes, Kara White; Sip, Christopher G.; Obenza, Willimark; Yang, Emily; Horst, Cody; Welikson, Robert E.; Hauschka, Stephen D.; Folch, Albert

2013-01-01

An improved understanding of the factors that regulate the migration of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) would provide new insights into human heart development and suggest novel strategies to improve their electromechanical integration after intracardiac transplantation. Since nothing has been reported as to the factors controlling hESC-CM migration, we hypothesized that hESC-CMs would migrate in response to the extracellular matrix and soluble signaling molecules previously implicated in heart morphogenesis. To test this, we screened candidate factors by transwell assay for effects on hESC-CM motility, followed by validation via live-cell imaging and/or gap-closure assays. Fibronectin (FN) elicited a haptotactic response from hESC-CMs, with cells seeded on a steep FN gradient showing nearly a fivefold greater migratory activity than cells on uniform FN. Studies with neutralizing antibodies indicated that adhesion and migration on FN are mediated by integrins α-5 and α-V. Next, we screened 10 soluble candidate factors by transwell assay and found that the noncanonical Wnt, Wnt5a, elicited an approximately twofold increase in migration over controls. This effect was confirmed using the gap-closure assay, in which Wnt5a-treated hESC-CMs showed approximately twofold greater closure than untreated cells. Studies with microfluidic-generated Wnt5a gradients showed that this factor was chemoattractive as well as chemokinetic, and Wnt5a-mediated responses were inhibited by the Frizzled-1/2 receptor antagonist, UM206. In summary, hESC-CMs show robust promigratory responses to FN and Wnt5a, findings that have implications on both cardiac development and cell-based therapies. PMID:23517131

Dynamical electron diffraction simulation for non-orthogonal crystal system by a revised real space method.

PubMed

Lv, C L; Liu, Q B; Cai, C Y; Huang, J; Zhou, G W; Wang, Y G

2015-01-01

In the transmission electron microscopy, a revised real space (RRS) method has been confirmed to be a more accurate dynamical electron diffraction simulation method for low-energy electron diffraction than the conventional multislice method (CMS). However, the RRS method can be only used to calculate the dynamical electron diffraction of orthogonal crystal system. In this work, the expression of the RRS method for non-orthogonal crystal system is derived. By taking Na2 Ti3 O7 and Si as examples, the correctness of the derived RRS formula for non-orthogonal crystal system is confirmed by testing the coincidence of numerical results of both sides of Schrödinger equation; moreover, the difference between the RRS method and the CMS for non-orthogonal crystal system is compared at the accelerating voltage range from 40 to 10 kV. Our results show that the CMS method is almost the same as the RRS method for the accelerating voltage above 40 kV. However, when the accelerating voltage is further lowered to 20 kV or below, the CMS method introduces significant errors, not only for the higher-order Laue zone diffractions, but also for zero-order Laue zone. These indicate that the RRS method for non-orthogonal crystal system is necessary to be used for more accurate dynamical simulation when the accelerating voltage is low. Furthermore, the reason for the increase of differences between those diffraction patterns calculated by the RRS method and the CMS method with the decrease of the accelerating voltage is discussed. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Short- and long-term effects of stress during adolescence on emotionality and HPA function of animals exposed to alcohol prenatally

PubMed Central

Raineki, Charlis; Chew, Leanne; Mok, Perry; Ellis, Linda; Weinberg, Joanne

2016-01-01

Prenatal alcohol exposure (PAE) is associated with extremely high rates of psychopathologies, which may be mediated by the hypothalamic-pituitary-adrenal (HPA) dysregulation observed in exposed individuals. Of relevance, PAE carries an increased risk of exposure to stressful environments throughout life. Importantly, stressful experiences during adolescence increase vulnerability to psychopathologies. However, little is known about how adolescent stressful experiences in the context of PAE-induced HPA dysregulation may further alter the developmental trajectory and potentially contribute to the disproportionally high rate of psychopathologies observed in this population. Here we investigate the short-and long-term effects of adolescent chronic mild stress (CMS) on the emergence of anxiety-/depressive-like behaviors (open-field and forced swim test - FST) and on HPA activity (corticosterone and type 1 CRH receptor – CRHR1) in PAE male and female rats. Under non-CMS conditions, open field results indicate that PAE induced inappropriate behavior (increased time in center) in males and females, with increased activity in female adolescents, but anxiety-like behavior in adult PAE females. Conversely, FST results indicate that PAE induced depressive-like behavior in adolescent males. Exposure to CMS resulted in increased activity in adolescent males and anxiety-like behaviors in adult females. Moreover, PAE and/or CMS altered corticosterone and CRHR1 expression in the mPFC and amygdala. Together, these results suggest that PAE and adolescent CMS induce dynamic neurobehavioral alterations that manifest differently depending on the age and sex of the animal. These results highlight the importance of using both sexes as well as an ontogenetic approach when investigating the effects of environmental adversity. PMID:27567117

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.

[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.

Automation of diagnostic genetic testing: mutation detection by cyclic minisequencing.

PubMed

Alagrund, Katariina; Orpana, Arto K

2014-01-01

The rising role of nucleic acid testing in clinical decision making is creating a need for efficient and automated diagnostic nucleic acid test platforms. Clinical use of nucleic acid testing sets demands for shorter turnaround times (TATs), lower production costs and robust, reliable methods that can easily adopt new test panels and is able to run rare tests in random access principle. Here we present a novel home-brew laboratory automation platform for diagnostic mutation testing. This platform is based on the cyclic minisequecing (cMS) and two color near-infrared (NIR) detection. Pipetting is automated using Tecan Freedom EVO pipetting robots and all assays are performed in 384-well micro plate format. The automation platform includes a data processing system, controlling all procedures, and automated patient result reporting to the hospital information system. We have found automated cMS a reliable, inexpensive and robust method for nucleic acid testing for a wide variety of diagnostic tests. The platform is currently in clinical use for over 80 mutations or polymorphisms. Additionally to tests performed from blood samples, the system performs also epigenetic test for the methylation of the MGMT gene promoter, and companion diagnostic tests for analysis of KRAS and BRAF gene mutations from formalin fixed and paraffin embedded tumor samples. Automation of genetic test reporting is found reliable and efficient decreasing the work load of academic personnel.

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...

Collective acceleration of laser plasma in a nonstationary and nonuniform magnetic field

NASA Astrophysics Data System (ADS)

Isaev, A.; Kozlovskiy, K.; Shikanov, A.; Vovchenko, E.

2017-12-01

This paper presents the new experimental results concerning acceleration of deuterium ions extracted from laser plasma in the rapid-growing nonuniform magnetic field in order to initiate the nuclear reactions D(d, n)3He and T(d, n)4He. For obtaining of laser plasma a Nd: YAG laser (λ = 1,06 μm) that generates in Q-switched mode the radiation pulses with the energy W ≤ 0,85 J and duration of τ ≈ 10 ns was used. Rapid-growing magnetic field was created with the discharge of Arkadyev-Marx pulsed-voltage generator to conical coil with the inductance of 0,65 μΗ. At characteristic discharge time of 30 ns, the rate of magnetic field growth achieved 2·107 T/s. Ion velocity was determined with the time-of-flight technique. During the experiment on deuterium plasma an ion flux velocity of ∼3 · 108 cm/s was obtained, which corresponds to the deuteron energy of ∼100 keV. Herewith, for target power density of ∼5·1011 W/cm2 obtaining of up to 1015 of accelerated deuterons and up to 108 of neutrons per a pulse is expected.

The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARγ-mediated alteration of microglial activation phenotypes.

PubMed

Zhao, Qiuying; Wu, Xiaohui; Yan, Shuo; Xie, Xiaofang; Fan, Yonghua; Zhang, Jinqiang; Peng, Cheng; You, Zili

2016-10-04

Discoveries that microglia-mediated neuroinflammation is involved in the pathological process of depression provided a new strategy for novel antidepressant therapy. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor regulating inflammation and microglial polarization and, therefore, a potential target for resolving depressive disorders. Our hypothesis was that antidepressant effects could be achieved through anti-inflammatory and neuroprotective activities by PPARγ-dependent microglia-modulating agents. Chronic mild stress (CMS) treatment was performed on C57BL/6 mice for 6 weeks. After 3 weeks with the CMS procedure, depressive-like behaviors were evaluated by sucrose preference (SP), tail suspension test (TST), forced swimming test (FST), and locomotor activity. Pioglitazone was administered intragastrically once per day for 3 weeks at different doses. Neuroinflammatory cytokines were determined by real time-PCR (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot. The activated microglial state was confirmed by immunohistochemistry. N9 microglial cells were subjected to lipopolysaccharide, pioglitazone, and GW9662 to discuss the phenotype of activated microglia by RT-PCR, ELISA, and western blot. It was demonstrated that the PPARγ agonist pioglitazone (2.5 mg/kg) ameliorated depression-like behaviors in CMS-treated mice, as indicated by body weight (BW), the SP test, the FST, and the TST. The amelioration of the depression was blocked by the PPARγ antagonist GW9662. The expression of M1 markers (IL-1β, IL-6, TNFα, iNOS, and CCL2) increased, and the gene expression of M2 markers (Ym1, Arg1, IL-4, IL-10, and TGFβ) decreased in the hippocampus of the stress-treated mice. Pioglitazone significantly inhibited the increased numbers and morphological alterations of microglia in the hippocampus, reduced the elevated expression of microglial M1 markers, and increased the downgraded expression of microglial M2 markers in C57BL/6 mice exposed to CMS. In an in vitro experiment, pioglitazone reversed the imbalance of M1 and M2 inflammatory cytokines, which is correlated with the inhibition of nuclear factor kB activation and is expressed in LPS-stimulated N9 microglial cells. We showed that pioglitazone administration induce the neuroprotective phenotype of microglia and ameliorate depression-like behaviors in CMS-treated C57BL/6 mice. These data suggested that the microglia-modulating agent pioglitazone present a beneficial choice for depression.

Conceptual study of the cryostats for the cold powering system for the triplets of the High Luminosity LHC

NASA Astrophysics Data System (ADS)

Ballarino, A.; Giannelli, S.; Jacquemod, A.; Leclercq, Y.; Ortiz Ferrer, C.; Parma, V.

2017-12-01

The High Luminosity LHC (HL-LHC) is a project aiming to upgrade the Large Hadron Collider (LHC) after 2020-2025 in order to increase the integrated luminosity by about one order of magnitude and extend the operational capabilities until 2035. The upgrade of the focusing triplet insertions for the Atlas and CMS experiments foresees using superconducting magnets operating in a pressurised superfluid helium bath at 1.9 K. The increased radiation levels from the particle debris produced by particle collisions in the experiments require that the power converters are placed in radiation shielded zones located in a service gallery adjacent to the main tunnel. The powering of the magnets from the gallery is achieved by means of MgB2 superconducting cables in a 100-m long flexible cryostat transfer line, actively cooled by 4.5 K to 20 K gaseous helium generated close to the magnets. At the highest temperature end, the helium flow cools the High Temperature Superconducting (HTS) current leads before being recovered at room temperature. At the magnet connection side, a dedicated connection box allows connection to the magnets and a controlled boil-off production of helium for the cooling needs of the powering system. This paper presents the overall concept of the cryostat system from the magnet connection boxes, through the flexible cryostat transfer line, to the connection box of the current leads.

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.

Self-referral of imaging and increased utilization: some practical perspectives on tackling the dilemma.

PubMed

Romano, Donald H

2009-11-01

Health care costs are higher in the United States than in any other country in the world, and imaging services have been growing much more rapidly than other services. Studies have shown a tendency for increased utilization of services, including imaging services, when referring physicians have ownership interest in the services. In recent years, the CMS has taken some action with respect to how it pays for imaging, including reducing physician payments when multiple images are taken on contiguous body parts during the same visit, establishing a cap on payments for certain imaging services, and imposing an antimarkup rule on diagnostic tests. In addition, CMS has made some changes to the Stark rules, which included adding nuclear medicine to the list of designated health services, prohibiting certain per-service or per-click leasing arrangements, and prohibiting physicians from owning entities that sell services to providers that then bill for them under arrangements. Because it is unclear whether these policy changes will have much effect on imaging utilization, CMS will continue to seek new ways to rein in utilization. In the near future, CMS and the US Department of Health and Human Services are likely to attempt to curb utilization not only through postpayment review and education but also through its various initiatives on improving the quality of services furnished to Medicare benificiaries.

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.

Magnetic Materials Characterization and Modeling for the Enhanced Design of Magnetic Shielding of Cryomodules in Particle Accelerators

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

Sah, Sanjay

Particle accelerators produce beams of high-energy particles, which are used for both fundamental and applied scientific research and are critical to the development of accelerator driven sub-critical reactor systems. An effective magnetic shield is very important to achieve higher quality factor (Qo) of the cryomodule of a particle accelerator. The allowed value of field inside the cavity due to all external fields (particularly the Earth’s magnetic field) is ~15 mG or less. The goal of this PhD dissertation is to comprehensively study the magnetic properties of commonly used magnetic shielding materials at both cryogenic and room temperatures. This knowledge canmore » be used for the enhanced design of magnetic shields of cryomodes (CM) in particle accelerators. To this end, we first studied the temperature dependent magnetization behavior (M-H curves) of Amumetal and A4K under different annealing and deformation conditions. This characterized the effect of stress or deformation induced during the manufacturing processes and subsequent restoration of high permeability with appropriate heat treatment. Next, an energy based stochastic model for temperature dependent anhysteretic magnetization behavior of ferromagnetic materials was proposed and benchmarked against experimental data. We show that this model is able to simulate and explain the magnetic behavior of as rolled, deformed and annealed amumetal and A4K over a large range of temperatures. The experimental results for permeability are then used in a finite element model (FEM) in COMSOL to evaluate the shielding effectiveness of multiple shield designs at room temperature as well as cryogenic temperature. This work could serve as a guideline for future design, development and fabrication of magnetic shields of CMs.« less

42 CFR 423.509 - Termination of contract by CMS.

Code of Federal Regulations, 2014 CFR

2014-10-01

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

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

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

ERIC Educational Resources Information Center

Gannon, Theresa A.

2006-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

45 CFR 150.347 - Failure to request a hearing.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

42 CFR 411.379 - When CMS accepts a request.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

42 CFR 405.1834 - CMS reviewing official procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

42 CFR 457.1003 - CMS review of waiver requests.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

PubMed

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

2015-01-15

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

CMS Analysis School Model

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

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

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

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

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

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

PubMed

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

2015-10-01

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

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

PubMed

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

2018-03-12

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

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

PubMed

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

2018-01-01

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

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

PubMed

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

2008-09-01

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

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

PubMed

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

2017-06-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2015-03-21

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

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

PubMed

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

2015-09-01

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

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

PubMed Central

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

2008-01-01

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

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

PubMed Central

2012-01-01

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

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

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

NASA Technical Reports Server (NTRS)

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

2014-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

Cosmic ray modulation and merged interaction regions

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Goldstein, M. L.; Mcdonald, F. B.

1985-01-01

Beyond several AU, interactions among shocks and streams give rise to merged interaction regions in which the magnetic field is turbulent. The integral intensity of . 75 MeV/Nuc cosmic rays at Voyager is generally observed to decrease when a merged interaction region moves past the spacecraft and to increase during the passage of a rarefaction region. When the separation between interaction regions is relatively large, the cosmic ray intensity tends to increase on a scale of a few months. This was the case at Voyager 1 from July 1, 1983 to May 1, 1984, when the spacecraft moved from 16.7 to 19.6 AU. Changes in cosmic ray intensity were related to the magnetic field strength in a simple way. It is estimated that the diffusion coefficient in merged interaction regions at this distance is similar to 0.6 x 10 to the 22nd power sq cm/s.

Observation of Charge-Dependent Azimuthal Correlations in p-Pb Collisions and Its Implication for the Search for the Chiral Magnetic Effect.

PubMed

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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; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonjes, M B; Tonwar, S C; Abercrombie, D; Allen, B; 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; 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; 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; Evans, A; Finkel, A; Gude, 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; Bartek, R; Bloom, K; Claes, D R; Dominguez, A; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Malta Rodrigues, A; 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; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wang, R-J; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Kubik, A; Kumar, A; 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; 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; Mc Donald, J; Medvedeva, T; Mei, K; Mooney, M; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Svyatkovskiy, A; Tully, C; Zuranski, A; Malik, S; Barker, A; Barnes, V E; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; 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; 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; Agapitos, A; 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; 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; Rose, A; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Cowden, C; 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; Ojalvo, I; Perry, T; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-03-24

Charge-dependent azimuthal particle correlations with respect to the second-order event plane in p-Pb and PbPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV have been studied with the CMS experiment at the LHC. The measurement is performed with a three-particle correlation technique, using two particles with the same or opposite charge within the pseudorapidity range |η|<2.4, and a third particle measured in the hadron forward calorimeters (4.4<|η|<5). The observed differences between the same and opposite sign correlations, as functions of multiplicity and η gap between the two charged particles, are of similar magnitude in p-Pb and PbPb collisions at the same multiplicities. These results pose a challenge for the interpretation of charge-dependent azimuthal correlations in heavy ion collisions in terms of the chiral magnetic effect.

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

NASA Astrophysics Data System (ADS)

Dhawan, Satish; Sumner, Richard

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

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...

77 FR 40063 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... research studies and methodological tests) to improve communication with key CMS audiences. As new... referred to as the Social Marketing and Consumer Testing Item Bank. This item bank is designed to establish... telephone surveys. The other set is less structured and is designed for use in qualitative one-on-one and...

76 FR 10600 - Medicare Program; Public Meeting in Calendar Year 2011 for New Clinical Laboratory Tests Payment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-1347-N... method called ``cross-walking'' is used when a new test is determined to be comparable to an existing... either cross-walk or gap-fill. II. Format This meeting to receive comments and recommendations (including...

The phase 1 upgrade of the CMS Pixel Front-End Driver

NASA Astrophysics Data System (ADS)

Friedl, M.; Pernicka, M.; Steininger, H.

2010-12-01

The pixel detector of the CMS experiment at the LHC is read out by analog optical links, sending the data to 9U VME Front-End Driver (FED) boards located in the electronics cavern. There are plans for the phase 1 upgrade of the pixel detector (2016) to add one more layer, while significantly cutting down the overall material budget. At the same time, the optical data transmission will be replaced by a serialized digital scheme. A plug-in board solution with a high-speed digital optical receiver has been developed for the Pixel-FED readout boards and will be presented along with first tests of the future optical link.

A pulse NMR study of water exchange across the erythrocyte membrane

NASA Astrophysics Data System (ADS)

Lahajnar, G.

1993-03-01

A pulse nuclear magnetic resonance (NMR) technique is employed to study the temperature dependence (5-40°C) of the diffusional water exchange time τexch for normal and p-hydroxymercuribenzoate ( p-HMB) treated bovine erythrocytes. The Arrhenius plot of τexch for normal erythrocytes implies the activation energy Ea of 20.4 kJ/mol, similar to that for self-diffusion of water ( Ea = 19.3 - 20.1 kJ/mol), and the value τexch of 12.5 ms at 20°C corresponds to the cell membrane diffusional water permeability coefficient P d of 3.6 × 10 -3 cm/s. The data for p-HMB treated cells display lengthening of τexch (i.e., τexch = 17.3 ms at 20°C) and increased E a of 29.0 kJ/mol. This E a value and a permeability coefficient P d of 2.6 × 10 -3 cm/s at 20°C, if compared to corresponding data for artificial lipid bilayer membranes, indicate either incomplete closure of the specialized water-selective protein channels on binding of p-HMB to their SH-groups, or complete channel closure plus new leaks.

Pushing HTCondor and glideinWMS to 200K+ Jobs in a Global Pool for CMS before Run 2

NASA Astrophysics Data System (ADS)

Balcas, J.; Belforte, S.; Bockelman, B.; Gutsche, O.; Khan, F.; Larson, K.; Letts, J.; Mascheroni, M.; Mason, D.; McCrea, A.; Saiz-Santos, M.; Sfiligoi, I.

2015-12-01

The CMS experiment at the LHC relies on HTCondor and glideinWMS as its primary batch and pilot-based Grid provisioning system. So far we have been running several independent resource pools, but we are working on unifying them all to reduce the operational load and more effectively share resources between various activities in CMS. The major challenge of this unification activity is scale. The combined pool size is expected to reach 200K job slots, which is significantly bigger than any other multi-user HTCondor based system currently in production. To get there we have studied scaling limitations in our existing pools, the biggest of which tops out at about 70K slots, providing valuable feedback to the development communities, who have responded by delivering improvements which have helped us reach higher and higher scales with more stability. We have also worked on improving the organization and support model for this critical service during Run 2 of the LHC. This contribution will present the results of the scale testing and experiences from the first months of running the Global Pool.

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

PubMed

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

2017-06-15

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

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2001-01-01

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

Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

PubMed

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

2015-12-30

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

42 CFR 416.30 - Terms of agreement with CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

ERIC Educational Resources Information Center

Korchmaros, Josephine D.; Gump, Nathaniel W.

2009-01-01

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

Recent Highlights of Metabolomics in Chinese Medicine Syndrome Research

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2016-01-01

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

CMS Analysis School Model

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

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

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

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

PubMed

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

2018-03-13

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

Manipulating Neutral Atoms in Chip-Based Magnetic Traps

NASA Technical Reports Server (NTRS)

Aveline, David; Thompson, Robert; Lundblad, Nathan; Maleki, Lute; Yu, Nan; Kohel, James

2009-01-01

Several techniques for manipulating neutral atoms (more precisely, ultracold clouds of neutral atoms) in chip-based magnetic traps and atomic waveguides have been demonstrated. Such traps and waveguides are promising components of future quantum sensors that would offer sensitivities much greater than those of conventional sensors. Potential applications include gyroscopy and basic research in physical phenomena that involve gravitational and/or electromagnetic fields. The developed techniques make it possible to control atoms with greater versatility and dexterity than were previously possible and, hence, can be expected to contribute to the value of chip-based magnetic traps and atomic waveguides. The basic principle of these techniques is to control gradient magnetic fields with suitable timing so as to alter a trap to exert position-, velocity-, and/or time-dependent forces on atoms in the trap to obtain desired effects. The trap magnetic fields are generated by controlled electric currents flowing in both macroscopic off-chip electromagnet coils and microscopic wires on the surface of the chip. The methods are best explained in terms of examples. Rather than simply allowing atoms to expand freely into an atomic waveguide, one can give them a controllable push by switching on an externally generated or a chip-based gradient magnetic field. This push can increase the speed of the atoms, typically from about 5 to about 20 cm/s. Applying a non-linear magnetic-field gradient exerts different forces on atoms in different positions a phenomenon that one can exploit by introducing a delay between releasing atoms into the waveguide and turning on the magnetic field.

Cerebral cavernous malformations: natural history and clinical management.

PubMed

Gross, Bradley A; Du, Rose

2015-01-01

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

The CMS dataset bookkeeping service

NASA Astrophysics Data System (ADS)

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

2008-07-01

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

An advanced look at surgical performance under Medicare's hospital-inpatient value-based purchasing program: who is winning and who is losing?

PubMed

Dupree, James M; Neimeyer, Jennifer; McHugh, Megan

2014-01-01

The Centers for Medicare and Medicaid Services (CMS) is beginning to shift from paying providers based on volume to more explicitly rewarding quality of care. The hospital value-based purchasing (VBP) program is the first in a series of mandatory programs to financially reward and penalize US hospitals based on quality measure performance. Our objective was to identify the characteristics of hospitals that perform well (and those that perform poorly) on the surgical measures in CMS' hospital VBP program. Using 2008 to 2010 performance data from CMS' Hospital Compare website and the 2009 American Hospital Association annual survey, we examined surgical measure performance for all acute care general hospitals in the US. Outcomes were determined by a composite surgical performance score indicating the percentage of eligible surgical performance points that a hospital received. There were 3,030 hospitals included in our study. Composite surgical performance scores were 15.6% lower at public hospitals than at for-profit hospitals (p < 0.01). Additionally, there were significant differences in the routes by which hospitals achieved points, with smaller hospitals, for-profit hospitals, Magnet hospitals, and NSQIP hospitals all more likely to obtain points via the achievement route. The results of our study indicate that public hospitals perform worse on the surgical measures in the hospital VBP program. This study raises important questions about the impact that this new, mandatory program will have on public hospitals, which serve an important safety-net role and appear to be disadvantaged in the hospital VBP program. This issue should continue to be investigated as these mandatory quality programs are updated in future years. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

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

Horizontal gene transfer of acetyltransferases, invertases and chorismate mutases from different bacteria to diverse recipients.

PubMed

Noon, Jason B; Baum, Thomas J

2016-04-12

Hoplolaimina plant-parasitic nematodes (PPN) are a lineage of animals with many documented cases of horizontal gene transfer (HGT). In a recent study, we reported on three likely HGT candidate genes in the soybean cyst nematode Heterodera glycines, all of which encode secreted candidate effectors with putative functions in the host plant. Hg-GLAND1 is a putative GCN5-related N-acetyltransferase (GNAT), Hg-GLAND13 is a putative invertase (INV), and Hg-GLAND16 is a putative chorismate mutase (CM), and blastp searches of the non-redundant database resulted in highest similarity to bacterial sequences. Here, we searched nematode and non-nematode sequence databases to identify all the nematodes possible that contain these three genes, and to formulate hypotheses about when they most likely appeared in the phylum Nematoda. We then performed phylogenetic analyses combined with model selection tests of alternative models of sequence evolution to determine whether these genes were horizontally acquired from bacteria. Mining of nematode sequence databases determined that GNATs appeared in Hoplolaimina PPN late in evolution, while both INVs and CMs appeared before the radiation of the Hoplolaimina suborder. Also, Hoplolaimina GNATs, INVs and CMs formed well-supported clusters with different rhizosphere bacteria in the phylogenetic trees, and the model selection tests greatly supported models of HGT over descent via common ancestry. Surprisingly, the phylogenetic trees also revealed additional, well-supported clusters of bacterial GNATs, INVs and CMs with diverse eukaryotes and archaea. There were at least eleven and eight well-supported clusters of GNATs and INVs, respectively, from different bacteria with diverse eukaryotes and archaea. Though less frequent, CMs from different bacteria formed supported clusters with multiple different eukaryotes. Moreover, almost all individual clusters containing bacteria and eukaryotes or archaea contained species that inhabit very similar niches. GNATs were horizontally acquired late in Hoplolaimina PPN evolution from bacteria most similar to the saprophytic and plant-pathogenic actinomycetes. INVs and CMs were horizontally acquired from bacteria most similar to rhizobacteria and Burkholderia soil bacteria, respectively, before the radiation of Hoplolaimina. Also, these three gene groups appear to have been frequent subjects of HGT from different bacteria to numerous, diverse lineages of eukaryotes and archaea, which suggests that these genes may confer important evolutionary advantages to many taxa. In the case of Hoplolaimina PPN, this advantage likely was an improved ability to parasitize plants.

Systematic evidence-based quality measurement life-cycle approach to measure retirement in CHIPRA.

PubMed

Dougherty, Denise; Mistry, Kamila B; Lindly, Olivia; Desoto, Maushami; LLanos, Karen; Chesley, Francis

2014-01-01

In 2009, Centers for Medicare and Medicaid Services (CMS) publicly released an initial child core set (CCS) of health care quality measures for voluntary reporting by state Medicaid and Children's Health Insurance Program (CHIP) programs. CMS is responsible for implementing the reporting program and for updating the CCS annually. We assessed selected CCS measures for potential retirement. We identified a 23-member external advisory group to provide relevant expertise. We worked with the group to identify 4 major criteria with multiple subcomponents for assessing the measures. We provided information corresponding to each criterion and subcriterion, using a variety of sources such as the 2009 Medicaid Analytic eXtract (MAX), state-level Medicaid and CHIP data submitted to the CMS, and summaries of published literature on clinical and quality improvement effectiveness related to the CCS topics. Using this information, the group: 1) used a modified Delphi process to score the measures in 2 anonymous scoring rounds (on a scale of 1 to 9 in each round); 2) voted on whether each measure should be retired; and 3) provided narrative explanations of their choices (which formed the basis of our qualitative findings). Recommendations were reviewed by CMS before promulgation to state programs. The Subcommittee of the National Advisory Council on Healthcare Research and Quality (SNAC) recommended that the 4 major criteria be importance, scientific acceptability, feasibility, and usability. The SNAC recommended 3 measures for retirement: access to primary care; testing for strep before recommending antibiotics for pharyngitis; and annual HbA1c testing of children with diabetes. Explanations for suggesting retirement of the measures included: views that the well-visit measures were a better measure of access than the primary care measure; a likely ceiling effect (pharyngitis); and the paucity of clinical evidence and low prevalence (both for HbA1c). CMS recommended that state Medicaid and CHIP programs retire 2 of the recommended measures from the CCS, but retained the access to primary care measure. Periodic reassessment of the value of health care quality measures can reduce reporting burden and allow measure users to focus on measures with higher likelihood of leading to improvements in quality of care and child health outcomes. Published by Elsevier Inc.

40 CFR Table 7 to Subpart Lllll of... - Applicability of General Provisions to Subpart LLLLL

Code of Federal Regulations, 2010 CFR

2010-07-01

... approval procedures 3. Performance audit requirements 4. Internal and external QA procedures for testing.... Keep old versions for 5 years after revisions No; § 63.8688 specifies the CMS requirements. § 63.8(e...

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.

Moving beyond the comprehensive in vitro proarrhythmia assay: Use of human-induced pluripotent stem cell-derived cardiomyocytes to assess contractile effects associated with drug-induced structural cardiotoxicity.

PubMed

Yang, Xi; Papoian, Thomas

2018-02-27

Drug-induced cardiotoxicity is a potentially severe side effect that can adversely affect myocardial contractility through structural or electrophysiological changes in cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising human cardiac in vitro model system to assess both proarrhythmic and non-proarrhythmic cardiotoxicity of new drug candidates. The scalable differentiation of hiPSCs into cardiomyocytes provides a renewable cell source that overcomes species differences present in current animal models of drug toxicity testing. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative represents a paradigm shift for proarrhythmic risk assessment, and hiPSC-CMs are an integral component of that paradigm. The recent advancements in hiPSC-CMs will not only impact safety decisions for possible drug-induced proarrhythmia, but should also facilitate risk assessment for non-proarrhythmic cardiotoxicity, where current non-clinical approaches are limited in detecting this risk before initiation of clinical trials. Importantly, emerging evidence strongly suggests that the use of hiPSC-CMs with cardiac physiological relevant measurements in vitro improves the detection of structural cardiotoxicity. Here we review high-throughput drug screening using the hiPSC-CM model as an experimentally feasible approach to assess potential contractile and structural cardiotoxicity in early phase drug development. We also suggest that the assessment of structural cardiotoxicity can be added to electrophysiological tests in the same platform to complement the Comprehensive in vitro Proarrhythmia Assay for regulatory use. Ideally, application of these novel tools in early drug development will allow for more reliable risk assessment and lead to more informed regulatory decisions in making safe and effective drugs available to the public. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

DTIC Science & Technology

2015-11-04

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

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

PubMed

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

2013-06-01

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

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

PubMed

Smeby, J; Sveen, A; Merok, M A; Danielsen, S A; Eilertsen, I A; Guren, M G; Dienstmann, R; Nesbakken, A; Lothe, R A

2018-05-01

The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMSs) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600). A subset was analyzed for gene expression and confident CMS classification was obtained for 317 samples. This cohort was expanded with clinical and molecular data, including CMS classification, from 514 patients in the publically available dataset GSE39582. Gene expression signatures associated with KRAS and BRAFV600E mutations were used to evaluate differential impact of mutations on gene expression among the CMS groups. BRAFV600E and KRAS mutations were both associated with inferior 5-year overall survival (OS) exclusively in MSS tumors (BRAFV600E mutation versus KRAS/BRAF wild-type: Hazard ratio (HR) 2.85, P < 0.001; KRAS mutation versus KRAS/BRAF wild-type: HR 1.30, P = 0.013). BRAFV600E-mutated MSS tumors were strongly enriched and associated with metastatic disease in CMS1, leading to negative prognostic impact in this subtype (OS: BRAFV600E mutation versus wild-type: HR 7.73, P = 0.001). In contrast, the poor prognosis of KRAS mutations was limited to MSS tumors with CMS2/CMS3 epithelial-like gene expression profiles (OS: KRAS mutation versus wild-type: HR 1.51, P = 0.011). The subtype-specific prognostic associations were substantiated by differential effects of BRAFV600E and KRAS mutations on gene expression signatures according to the MSI status and CMS group. BRAFV600E mutations are enriched and associated with metastatic disease in CMS1 MSS tumors, leading to poor prognosis in this subtype. KRAS mutations are associated with adverse outcome in epithelial (CMS2/CMS3) MSS tumors.

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

PubMed Central

Triscoli, Chantal; Ackerley, Rochelle; Sailer, Uta

2014-01-01

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

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.

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.

Purification of Cardiomyocytes from Differentiating Pluripotent Stem Cells using Molecular Beacons Targeting Cardiomyocyte-Specific mRNA

PubMed Central

Kim, Sangsung; Park, Hun-Jun; Byun, Jaemin; Cho, Kyu-Won; Saafir, Talib; Song, Ming-Ke; Yu, Shan Ping; Wagner, Mary; Bao, Gang; Yoon, Young-Sup

2013-01-01

Background While methods for generating cardiomyocytes (CMs) from pluripotent stem cells (PSCs) have been reported, current methods produce heterogeneous mixtures of CMs and non-CM cells. Here, we report an entirely novel system in which PSC-derived CMs are purified by CM-specific molecular beacons (MBs). MBs are nano-scale probes that emit a fluorescence signal when hybridized to target mRNAs. Method and Results Five MBs targeting mRNAs of either cardiac troponin T or myosin heavy chain 6/7 were generated. Among five MBs, a MB targeting myosin heavy chain 6/7 mRNA (MHC1-MB) identified up to 99% of HL-1 CMs, a mouse CM cell line, but < 3% of four non-CM cell types in flow cytometry analysis, indicating that MHC1-MB is specific for identifying CMs. We delivered MHC1-MB into cardiomyogenically differentiated PSCs through nucleofection. The detection rate of CMs was similar to the percentages of cardiac troponin T (TNNT2) or cardiac troponin I (TNNI3)-positive CMs, supporting the specificity of MBs. Finally, MHC1-MB-positive cells were FACS-sorted from mouse and human PSC differentiating cultures and ~97% cells expressed TNNT2- or TNNI3 determined by flow cytometry. These MB-based sorted cells maintained their CM characteristics verified by spontaneous beating, electrophysiologic studies, and expression of cardiac proteins. When transplanted in a myocardial infarction model, MB-based purified CMs improved cardiac function and demonstrated significant engraftment for 4 weeks without forming tumors. Conclusions We developed a novel CM selection system that allows production of highly purified CMs. These purified CMs and this system can be valuable for cell therapy and drug discovery. PMID:23995537

Reporting trends and outcomes in ST-segment-elevation myocardial infarction national hospital quality assessment programs.

PubMed

McCabe, James M; Kennedy, Kevin F; Eisenhauer, Andrew C; Waldman, Howard M; Mort, Elizabeth A; Pomerantsev, Eugene; Resnic, Frederic S; Yeh, Robert W

2014-01-14

For patients who undergo primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction, the door-to-balloon time is an important performance measure reported to the Centers for Medicare & Medicaid Services (CMS) and tied to hospital quality assessment and reimbursement. We sought to assess the use and impact of exclusion criteria associated with the CMS measure of door-to-balloon time in primary PCI. All primary PCI-eligible patients at 3 Massachusetts hospitals (Brigham and Women's, Massachusetts General, and North Shore Medical Center) were evaluated for CMS reporting status. Rates of CMS reporting exclusion were the primary end points of interest. Key secondary end points were between-group differences in patient characteristics, door-to-balloon times, and 1-year mortality rates. From 2005 to 2011, 26% (408) of the 1548 primary PCI cases were excluded from CMS reporting. This percentage increased over the study period from 13.9% in 2005 to 36.7% in the first 3 quarters of 2011 (P<0.001). The most frequent cause of exclusion was for a diagnostic dilemma such as a nondiagnostic initial ECG, accounting for 31.2% of excluded patients. Although 95% of CMS-reported cases met door-to-balloon time goals in 2011, this was true of only 61% of CMS-excluded cases and consequently 82.6% of all primary PCI cases performed that year. The 1-year mortality for CMS-excluded patients was double that of CMS-included patients (13.5% versus 6.6%; P<0.001). More than a quarter of patients who underwent primary PCI were excluded from hospital quality reports collected by CMS, and this percentage has grown substantially over time. These findings may have significant implications for our understanding of process improvement in primary PCI and mechanisms for reimbursement through Medicare.

Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

NASA Astrophysics Data System (ADS)

Zhao, Jing; Jung, Yang-Hee; Jang, Choon-Gon; Chun, Kwang-Hoon; Kwon, Sung Won; Lee, Jeongmi

2015-03-01

Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

Ajmaline blocks INa and IKr without eliciting differences between Brugada syndrome patient and control human pluripotent stem cell-derived cardiac clusters.

PubMed

Miller, Duncan C; Harmer, Stephen C; Poliandri, Ariel; Nobles, Muriel; Edwards, Elizabeth C; Ware, James S; Sharp, Tyson V; McKay, Tristan R; Dunkel, Leo; Lambiase, Pier D; Tinker, Andrew

2017-12-01

The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both I Na and I Kr . Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A sodium channel mutations), analysis of hiPSC-CMs from patients and controls revealed that differentiation and action potential parameters were similar. Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation-recovery interval consistently across all lines. We conclude that ajmaline can block both depolarisation and repolarisation of hiPSC-CMs at the cellular level, but that a more refined integrated tissue model may be necessary to elicit differences in its effect between BrS patients and controls. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Specific Detection of Clavibacter michiganensis subsp. sepedonicus by Amplification of Three Unique DNA Sequences Isolated by Subtraction Hybridization.

PubMed

Mills, D; Russell, B W; Hanus, J W

1997-08-01

ABSTRACT Three single-copy, unique DNA fragments, designated Cms50, Cms72, and Cms85, were isolated from strain CS3 of Clavibacter michiganensis subsp. sepedonicus by subtraction hybridization using driver DNA from C. michiganensis subsp. insidiosus, C. michiganensis subsp. michiganensis, and Rhodococcus facians. Radio-labeled probes made of these fragments and used in Southern blot analysis revealed each to be absolutely specific to all North American C. michiganensis subsp. sepedonicus strains tested, including plasmidless and nonmucoid strains. The probes have no homology with genomic DNA from related C. michiganensis subspecies insidiosus, michiganensis, and tessellarius, nor with DNA from 11 additional bacterial species and three unidentified strains, some of which have been previously reported to display cross-reactivity with C. michiganensis subsp. sepedonicus-specific antisera. The three fragments shared no homology, and they appeared to be separated from each other by at least 20 kbp in the CS3 genome. Internal primer sets permitted amplification of each fragment by the polymerase chain reaction (PCR) only from C. michiganensis subsp. sepedonicus DNA. In a PCR-based sensitivity assay using a primer set that amplifies Cms85, the lowest level of detection of C. michiganensis subsp. sepedonicus was 100 CFU per milliliter when cells were added to potato core fluid. Erroneous results that may arise from PCR artifacts and mutational events are, therefore, minimized by the redundancy of the primer sets, and the products should be verifiable with unique capture probes in sequence-based detection systems.

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.

Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling.

PubMed

Korfmacher, Walter; Luo, Yongyi; Ho, Stacy; Sun, Wei; Shen, Liduo; Wang, Jie; Wu, Zhongtao; Guo, Yang; Snow, Gregory; O'Shea, Thomas

2015-01-01

Serial sampling methods have been used for rat pharmacokinetic (PK) studies for over 20 years. Currently, it is still common to take 200-250 μL of blood at each timepoint when performing a PK study in rats and using serial sampling. While several techniques have been employed for collecting blood samples from rats, there is only limited published data to compare these methods. Recently, microsampling (≤ 50 μL) techniques have been reported as an alternative process for collecting blood samples from rats. In this report, five compounds were dosed orally into rats. For three proprietary compounds, jugular vein cannula (JVC) sampling was used to collect whole blood and plasma samples and capillary microsampling (CMS) was used to collect blood samples from the tail vein of the same animal. For the two other compounds, marketed drugs fluoxetine and glipizide, JVC sampling was used to collect both whole blood and blood CMS samples while tail-vein sampling from the same rats was also used to collect both whole blood and blood CMS samples. For the three proprietary compounds, the blood AUC as well as the blood concentration-time profile that were obtained from the tail vein were different from those obtained via JVC sampling. For fluoxetine, the blood total exposure (AUC) was not statistically different when comparing tail-vein sampling to JVC sampling, however the blood concentration-time profile that was obtained from the tail vein was different than the one obtained from JVC sampling. For glipizide, the blood AUC and concentration-time profile were not statistically different when comparing the tail-vein sampling to the JVC sampling. For both fluoxetine and glipizide, the blood concentration profiles obtained from CMS were equivalent to the blood concentration profiles obtained from the standard whole blood sampling, collected at the same sampling site. The data in this report provide strong evidence that blood CMS is a valuable small volume blood sampling approach for rats and that it provides results for test compound concentrations that are equivalent to those obtained from traditional whole blood sampling. The data also suggest that for some compounds, the concentration-time profile that is obtained for a test compound based on sampling from a rat tail vein may be different from that obtained from rat JVC sampling. In some cases, this shift in the concentration-time profile will result in different PK parameters for the test compound. Based on these observations, it is recommended that a consistent blood sampling method should be used for serial microsampling in discovery rat PK studies when testing multiple new chemical entities. If the rat tail vein sampling method is selected for PK screening, then conducting a bridging study on the lead compound is recommended to confirm that the rat PK obtained from JVC sampling is comparable to the tail-vein sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

Advanced strategies for quality control of Chinese medicines.

PubMed

Zhao, Jing; Ma, Shuang-Cheng; Li, Shao-Ping

2018-01-05

Quality control is always the critical issue for Chinese medicines (CMs) with their worldwide increasing use. Different from western medicine, CMs are usually considered that multiple constituents are responsible for the therapeutic effects. Therefore, quality control of CMs is a challenge. In 2011, the strategies for quantification, related to the markers, reference compounds and approaches, in quality control of CMs were reviewed (Li, et al., J. Pharm. Biomed. Anal., 2011, 55, 802-809). Since then, some new strategies have been proposed in these fields. Therefore, the review on the strategies for quality control of CMs should be updated to improve the safety and efficacy of CMs. Herein, novel strategies related to quality marker discovery, reference compound development and advanced approaches (focused on glyco-analysis) for quality control, during 2011-2016, were summarized and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Partial characterization of chayotextle starch-based films added with ascorbic acid encapsulated in resistant starch.

PubMed

Martínez-Ortiz, Miguel A; Vargas-Torres, Apolonio; Román-Gutiérrez, Alma D; Chavarría-Hernández, Norberto; Zamudio-Flores, Paul B; Meza-Nieto, Martín; Palma-Rodríguez, Heidi M

2017-05-01

Chayotextle starch was modified by subjecting it to a dual treatment with acid and heating-cooling cycles. This caused a decrease in the content of amylose, which showed values of 30.22%, 4.80%, 3.27% and 3.57% for native chayotextle starch (NCS), starch modified by acid hydrolysis (CMS), and CMS with one (CMS1AC) and three autoclave cycles (CMS3AC), respectively. The percentage of crystallinity showed an increase of 36.9%-62% for NCS and CMS3AC. The highest content of resistant starch (RS) was observed in CMS3AC (37.05%). The microcapsules were made with CMS3AC due to its higher RS content; the total content of ascorbic acid of the microcapsules was 82.3%. The addition of different concentrations of CMS3AC microcapsules (0%, 2.5%, 6.255% and 12.5%) to chayotextle starch-based films (CSF) increased their tensile strength and elastic modulus. The content of ascorbic acid and RS in CSF was ranged from 0% to 59.4% and from 4.84% to 37.05% in the control film and in the film mixed with CMS3AC microcapsules, respectively. Water vapor permeability (WVP) values decreased with increasing concentrations of microcapsules in the films. Microscopy observations showed that higher concentrations of microcapsules caused agglomerations due their poor distribution in the matrix of the films. Copyright © 2017 Elsevier B.V. All rights reserved.

Human cardiomyocyte generation from pluripotent stem cells: A state-of-art.

PubMed

Talkhabi, Mahmood; Aghdami, Nasser; Baharvand, Hossein

2016-01-15

The human heart is considered a non-regenerative organ. Worldwide, cardiovascular diseases continue to be the leading cause of death. Despite advances in cardiac treatment, myocardial repair remains severely limited by the lack of an appropriate source of viable cardiomyocytes (CMs) to replace damaged tissue. Human pluripotent stem cells (hPSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently be differentiated into functional CMs necessary for cell replacement therapy and other potential applications. The number of protocols that derive CMs from hPSCs has increased exponentially over the past decade following observation of the first human beating CMs. A number of highly efficient, chemical based protocols have been developed to generate human CMs (hCMs) in small-scale and large-scale suspension systems. To reduce the heterogeneity of hPSC-derived CMs, the differentiation protocols were modulated to exclusively generate atrial-, ventricular-, and nodal-like CM subtypes. Recently, remarkable advances have been achieved in hCM generation including chemical-based cardiac differentiation, cardiac subtype specification, large-scale suspension culture differentiation, and development of chemically defined culture conditions. These hCMs could be useful particularly in the context of in vitro disease modeling, pharmaceutical screening and in cellular replacement therapies once the safety issues are overcome. Herein we review recent progress in the in vitro generation of CMs and cardiac subtypes from hPSCs and discuss their potential applications and current limitations. Copyright © 2015 Elsevier Inc. All rights reserved.

Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.

PubMed

Chen, Ying-Jung; Liu, Wen-Hsin; Kao, Pei-Hsiu; Wang, Jeh-Jeng; Chang, Long-Sen

2010-06-15

CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom, induced apoptosis of human leukemia K562 cells, characterized by mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+ concentration and the production of reactive oxygen species (ROS) was noted. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS scavenger) proved that Ca2+ was an upstream event in inducing ROS generation. Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562 cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced drastically the cytotoxicity of CMS-9, and a combination of lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9. Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is catalytic activity-dependent and is mediated through mitochondria-mediated death pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation. 2010 Elsevier Ltd. All rights reserved.

Origin of the CMS gene locus in rapeseed cybrid mitochondria: active and inactive recombination produces the complex CMS gene region in the mitochondrial genomes of Brassicaceae.

PubMed

Oshima, Masao; Kikuchi, Rie; Imamura, Jun; Handa, Hirokazu

2010-01-01

CMS (cytoplasmic male sterile) rapeseed is produced by asymmetrical somatic cell fusion between the Brassica napus cv. Westar and the Raphanus sativus Kosena CMS line (Kosena radish). The CMS rapeseed contains a CMS gene, orf125, which is derived from Kosena radish. Our sequence analyses revealed that the orf125 region in CMS rapeseed originated from recombination between the orf125/orfB region and the nad1C/ccmFN1 region by way of a 63 bp repeat. A precise sequence comparison among the related sequences in CMS rapeseed, Kosena radish and normal rapeseed showed that the orf125 region in CMS rapeseed consisted of the Kosena orf125/orfB region and the rapeseed nad1C/ccmFN1 region, even though Kosena radish had both the orf125/orfB region and the nad1C/ccmFN1 region in its mitochondrial genome. We also identified three tandem repeat sequences in the regions surrounding orf125, including a 63 bp repeat, which were involved in several recombination events. Interestingly, differences in the recombination activity for each repeat sequence were observed, even though these sequences were located adjacent to each other in the mitochondrial genome. We report results indicating that recombination events within the mitochondrial genomes are regulated at the level of specific repeat sequences depending on the cellular environment.

Risk factors for cardiomyopathy syndrome (CMS) in Norwegian salmon farming.

PubMed

Bang Jensen, Britt; Brun, Edgar; Fineid, Birgitte; Larssen, Rolf Bjerke; Kristoffersen, Anja B

2013-12-12

Cardiomyopathy syndrome (CMS) has been an economically important disease in Norwegian aquaculture since the 1990s. In this study, data on monthly production characteristics and case registrations were combined in a cohort study and supplemented with a questionnaire-based case-control survey on management factors in order to identify risk factors for CMS. The cohort study included cases and controls from 2005 to 2012. From this dataset differences between all cases and controls were analyzed by a mixed effect multivariate logistic regression. From this we found that the probability of CMS increased with increasing time in the sea, infection pressure, and cohort size, and that cohorts which had previously been diagnosed with heart and skeletal muscle inflammation or which were in farms with a history of CMS in previous cohorts had double the odds of developing CMS. The model was then used to calculate the predicted value for each cohort from which additional data were obtained via the questionnaire-based survey and used as offset for calculating the probability of CMS in a semi-univariate analysis of additional risk factors. Finally, the model was used to calculate the probability of developing CMS in 100 different scenarios in which the cohorts were subject to increasingly worse conditions with regards to the risk factors from the dataset. We believe that this exercise is a good way of communicating the findings to farmers, so they can make informed decisions when trying to avoid CMS in their fish cohorts.

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

NASA Astrophysics Data System (ADS)

Jain, S.

2017-03-01

The High Granularity Calorimeter (HGCAL) is the technology choice of the CMS collaboration for the endcap calorimetry upgrade planned to cope with the harsh radiation and pileup environment at the High Luminosity-LHC . The HGCAL is realized as a sampling calorimeter, including an electromagnetic compartment comprising 28 layers of silicon pad detectors with pad areas of 0.5-01. cm2 interspersed with absorbers made from tungsten and copper to form a highly compact and granular device. Prototype modules, based on hexagonal silicon pad sensors, with 128 channels, have been constructed and tested in beams at FNAL and at CERN. The modules include many of the features required for this challenging detector, including a PCB glued directly to the sensor, using through-hole wire-bonding for signal readout and 5 mm spacing between layers—including the front-end electronics and all services. Tests in 2016 have used an existing front-end chip —Skiroc2 (designed for the CALICE experiment for ILC). We present results from first tests of these modules both in the laboratory and with beams of electrons, pions and protons, including noise performance, calibration with mips and electron signals.

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…

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 63.7191 - What records must I keep?

Code of Federal Regulations, 2010 CFR

2010-07-01

... malfunctions. (3) Records of performance tests and performance evaluations as required in § 63.10(b)(2)(viii... measurements, raw performance evaluation measurements). (3) All required CMS measurements (including monitoring... Section 63.7191 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...

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

PubMed

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

2004-07-12

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

Science on Drupal: An evaluation of CMS Technologies

NASA Astrophysics Data System (ADS)

Vinay, S.; Gonzalez, A.; Pinto, A.; Pascuzzi, F.; Gerard, A.

2011-12-01

We conducted an extensive evaluation of various Content Management System (CMS) technologies for implementing different websites supporting interdisciplinary science data and information. We chose two products, Drupal and Bluenog/Hippo CMS, to meet our specific needs and requirements. Drupal is an open source product that is quick and easy to setup and use. It is a very mature, stable, and widely used product. It has rich functionality supported by a large and active user base and developer community. There are many plugins available that provide additional features for managing citations, map gallery, semantic search, digital repositories (fedora), scientific workflows, collaborative authoring, social networking, and other functions. All of these work very well within the Drupal framework if minimal customization is needed. We have successfully implemented Drupal for multiple projects such as: 1) the Haiti Regeneration Initiative (http://haitiregeneration.org/); 2) the Consortium on Climate Risk in the Urban Northeast (http://beta.ccrun.org/); and 3) the Africa Soils Information Service (http://africasoils.net/). We are also developing two other websites, the Côte Sud Initiative (CSI) and Emerging Infectious Diseases, using Drupal. We are testing the Drupal multi-site install for managing different websites with one install to streamline the maintenance. In addition, paid support and consultancy for Drupal website development are available at affordable prices. All of these features make Drupal very attractive for implementing state-of-the-art scientific websites that do not have complex requirements. One of our major websites, the NASA Socioeconomic Data and Applications Center (SEDAC), has a very complex set of requirements. It has to easily re-purpose content across multiple web pages and sites with different presentations. It has to serve the content via REST or similar standard interfaces so that external client applications can access content in the CMS repository. This means the content repository and structure should be completely separated from the content presentation and site structure. In addition to the CMS repository, the front-end website has to be able to consume, integrate, and display diverse content flexibly from multiple back-end systems, including custom and legacy systems, such as Oracle, Geoserver, Flickr, Fedora, and other web services. We needed the ability to customize the workflow to author, edit, approve, and publish content based on different content types and project requirements. In addition, we required the ability to use the existing active directory for user management with support for roles and groups and permissions using Access Control List (ACL) model. The ability to version and lock content was also important. We determined that most of these capabilities are difficult to implement with Drupal and needed significant customization. The Bluenog eCMS (enterprise CMS) product satisfied most of these requirements. Bluenog eCMS is based on an open source product called Hippo with customizations and support provided by the vendor Bluenog. Our newly redesigned and recently released SEDAC website, http://sedac.ciesin.columbia.edu, is implemented using Bluenog eCMS. Other products we evaluated include WebLogic portal, Magnolia, Liferay portal, and Alfresco.