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Sample records for mammo-tomography cmt system

  1. Design, Implementation, and Characterization of a Dedicated Breast Computed Mammo Tomography System for Enhanced Lesion Imaging

    DTIC Science & Technology

    2007-03-01

    characteristics for dedicated breast CmT [3,4]; two other rare earth metals with similar K-edge energies, Europium and Neodynium are included as practical...Computed mammoTomography ( CmT ) solution we are proposing 2-10 has several potential benefits, including: (1) improved detection and characterization of...apparent that a fixed tilt CmT system was required and therefore it became necessary to investigate trade-offs 30º 20º Paxscan 2520 digital

  2. Design, Implementation, and Characterization of a Dedicated Breast Computed MammoTomography System for Enhanced Lesion Imaging

    DTIC Science & Technology

    2008-03-01

    this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data...sub-task details and progress are provided below. Some of this time was also spent providing guidance to the team for integration and development...the commercialization effort, and full time employment of the PI. 12 References [1] American Cancer Society, "Cancer Facts and Figures

  3. Types of CMT

    MedlinePlus

    ... Meet our Partners How to Get Involved Donate Charcot-Marie-Tooth Disease (CMT) Share print email share facebook twitter google ... get involved? Contact Us Get Our Emails About Charcot-Marie-Tooth Disease (CMT) Types Of Charcot-Marie-Tooth Disease (CMT) ...

  4. Cytotoxic activity and inhibition of tumor cell invasion by derivatives of a chemically modified tetracycline CMT-3 (COL-3).

    PubMed

    Lokeshwar, B L; Escatel, E; Zhu, B

    2001-02-01

    Tetracyclines such as chlortetracycline and doxycycline with antimicrobial activity were reported to possess cytostatic and cytotoxic activity against mammalian tumor cells, often at high doses. Non-antimicrobial chemically modified tetracyclines (CMTs), with limited systemic toxicity but with significant tumor cell toxicity and antimetastatic activity, are attractive for long term treatment for cancer. We recently reported one such CMT, 6-deoxy,6-demethyl 4-dedimethylamino tetracycline (CMT-3) is a potent anti-tumor and anti-metastatic drug. Here we report on the anti-cell proliferation and anti-invasive activity of five nitro derivatives of CMT-3 (CMT-3N). All the five CMT-3Ns (CMT-302, CMT-303, CMT-306, CMT-308 and CMT-316) inhibited in vitro cell proliferation of prostate cancer cells. The 50% growth inhibition concentration (IC(50)) of CMT-3Ns was similar to that of CMT-3. Although CMT-3 was by far the most potent anti-cell proliferation drug, all CMT-3Ns except CMT-303 and CMT-308 had similar anti-cell proliferation activity (IC(50): 2.5 -5.7 microg/ml). IC(50)s for CMT-303 and CMT-308 were approximately 8.1 and -12.4 microg/ml, respectively. Activity against tumor cell invasion was tested in vitro using the Matrigel invasion assay. All CMT-3Ns had similar anti- invasive activity. While cytotoxic activity of CMT-3 was strongly associated with cell death-effector caspase activation, mitochondrial permeablization and apoptosis, the CMT-3Ns weakly induced apoptosis and did not activate Caspase-3. However, the CMT-3Ns were able to induce mitochondrial permeabilization. This dichotomous mechanism of cytotoxic activity of CMTs may have significance in their selection for clinical application.

  5. An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients

    ClinicalTrials.gov

    2015-04-28

    Charcot Marie Tooth Disease (CMT); Hereditary Sensory and Motor Neuropathy; Nerve Compression Syndromes; Tooth Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System

  6. Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent.

    PubMed Central

    Timmerman, V; Rautenstrauss, B; Reiter, L T; Koeuth, T; Löfgren, A; Liehr, T; Nelis, E; Bathke, K D; De Jonghe, P; Grehl, H; Martin, J J; Lupski, J R; Van Broeckhoven, C

    1997-01-01

    Charcot-Marie-Tooth type 1 disease (CMT1) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system. The majority of CMT1 patients have a 1.5Mb tandem duplication (CMT1A) in chromosome 17p11.2 while most HNPP patients have a deletion of the same 1.5 Mb region. The CMT1A duplication and HNPP deletion are the reciprocal products of an unequal crossing over event between misaligned flanking CMT1A-REP elements. We analysed 162 unrelated CMT1A duplication patients and HNPP deletion patients from 11 different countries for the presence of a recombination hotspot in the CMT1A-REP sequences. A hotspot for unequal crossing over between the misaligned flanking CMT1A-REP elements was observed through the detection of novel junction fragments in 76.9% of 130 unrelated CMT1A patients and in 71.9% of 32 unrelated HNPP patients. This recombination hotspot was also detected in eight out of 10 de novo CMT1A duplication and in two de novo HNPP deletion patients. These data indicate that the hotspot of unequal crossing over occurs in several populations independently of ethnic background and is directly involved in the pathogenesis of CMT1A and HNPP. We conclude that the detection of junction fragments from the CMT1A-REP element on Southern blot analysis is a simple and reliable DNA diagnostic tool for the identification of the CMT1A duplication and HNPP deletion in most patients. Images PMID:9032649

  7. Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent.

    PubMed

    Timmerman, V; Rautenstrauss, B; Reiter, L T; Koeuth, T; Löfgren, A; Liehr, T; Nelis, E; Bathke, K D; De Jonghe, P; Grehl, H; Martin, J J; Lupski, J R; Van Broeckhoven, C

    1997-01-01

    Charcot-Marie-Tooth type 1 disease (CMT1) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system. The majority of CMT1 patients have a 1.5Mb tandem duplication (CMT1A) in chromosome 17p11.2 while most HNPP patients have a deletion of the same 1.5 Mb region. The CMT1A duplication and HNPP deletion are the reciprocal products of an unequal crossing over event between misaligned flanking CMT1A-REP elements. We analysed 162 unrelated CMT1A duplication patients and HNPP deletion patients from 11 different countries for the presence of a recombination hotspot in the CMT1A-REP sequences. A hotspot for unequal crossing over between the misaligned flanking CMT1A-REP elements was observed through the detection of novel junction fragments in 76.9% of 130 unrelated CMT1A patients and in 71.9% of 32 unrelated HNPP patients. This recombination hotspot was also detected in eight out of 10 de novo CMT1A duplication and in two de novo HNPP deletion patients. These data indicate that the hotspot of unequal crossing over occurs in several populations independently of ethnic background and is directly involved in the pathogenesis of CMT1A and HNPP. We conclude that the detection of junction fragments from the CMT1A-REP element on Southern blot analysis is a simple and reliable DNA diagnostic tool for the identification of the CMT1A duplication and HNPP deletion in most patients.

  8. Charcot Marie Tooth (CMT) Subtypes and Genetic Testing Strategies

    PubMed Central

    Saporta, Anita S.D.; Sottile, Stephanie L.; Miller, Lindsey J.; Feely, Shawna M.E.; Siskind, Carly E; Shy, Michael E.

    2010-01-01

    Background Charcot Marie Tooth disease (CMT) affects one in 2500 people and is caused by mutations in more than 30 genes. Identifying the genetic cause of CMT is often necessary for family planning, natural history studies and for entry into clinical trials. However genetic testing can be both expensive and confusing to patients and physicians. Methods We analyzed data from 1024 of our patients to determine the percentage and features of each CMT subtype within this clinic population. We identified distinguishing clinical and physiological features of the subtypes that could be used to direct genetic testing for patients with CMT. Findings Of 1024 patients evaluated, 787 received CMT diagnoses. Five hundred twenty-seven patients with CMT (67%) received a genetic subtype, while 260 did not have a mutation identified. The most common CMT subtypes were CMT1A, CMT1X, HNPP, CMT1B, and CMT2A. All other subtypes accounted for less than 1% each. Eleven patients had more than one genetically identified subtype of CMT. Patients with genetically identified CMT were separable into specific groups based on age of onset and the degree of slowing of motor nerve conduction velocities. Interpretation Combining features of the phenotypic and physiology groups allowed us to identify patients who were highly likely to have specific subtypes of CMT. Based on these results, we propose a strategy of focused genetic testing for CMT illustrated in a series of flow diagrams created as testing guides. PMID:21280073

  9. Proceedings of the workshop on high resolution computed microtomography (CMT)

    SciTech Connect

    1997-02-01

    The purpose of the workshop was to determine the status of the field, to define instrumental and computational requirements, and to establish minimum specifications required by possible users. The most important message sent by implementers was the remainder that CMT is a tool. It solves a wide spectrum of scientific problems and is complementary to other microscopy techniques, with certain important advantages that the other methods do not have. High-resolution CMT can be used non-invasively and non-destructively to study a variety of hierarchical three-dimensional microstructures, which in turn control body function. X-ray computed microtomography can also be used at the frontiers of physics, in the study of granular systems, for example. With high-resolution CMT, for example, three-dimensional pore geometries and topologies of soils and rocks can be obtained readily and implemented directly in transport models. In turn, these geometries can be used to calculate fundamental physical properties, such as permeability and electrical conductivity, from first principles. Clearly, use of the high-resolution CMT technique will contribute tremendously to the advancement of current R and D technologies in the production, transport, storage, and utilization of oil and natural gas. It can also be applied to problems related to environmental pollution, particularly to spilling and seepage of hazardous chemicals into the Earth's subsurface. Applications to energy and environmental problems will be far-ranging and may soon extend to disciplines such as materials science--where the method can be used in the manufacture of porous ceramics, filament-resin composites, and microelectronics components--and to biomedicine, where it could be used to design biocompatible materials such as artificial bones, contact lenses, or medication-releasing implants. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  10. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success

    PubMed Central

    Timmerman, Vincent; Strickland, Alleene V.; Züchner, Stephan

    2014-01-01

    Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs. PMID:24705285

  11. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success.

    PubMed

    Timmerman, Vincent; Strickland, Alleene V; Züchner, Stephan

    2014-01-22

    Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs.

  12. Causes of Charcot-Marie-Tooth Disease (CMT)

    MedlinePlus

    ... motor and sensory problems in the body’s extremities. Inheritance patterns in CMT Although CMT can look very similar ... from a parent will have the disease, as will the parent. When CMT is passed on in an autosomal dominant pattern, it can be easy to recognize in the ...

  13. Murine therapeutic models for Charcot-Marie-Tooth (CMT) disease.

    PubMed

    Fledrich, Robert; Stassart, Ruth M; Sereda, Michael W

    2012-06-01

    Charcot-Marie-Tooth (CMT) disease represents a broad group of inherited motor and sensory neuropathies which can originate from various genetic aberrations, e.g. mutations, deletions and duplications. We performed a literature review on murine animal models of CMT disease with regard to experimental therapeutic approaches. Hereby, we focussed on the demyelinating subforms of CMT (CMT1). PubMed items were CMT, animal model, demyelination and therapy. Patients affected by CMT suffer from slowly progressive, distally pronounced muscle atrophy caused by an axonal loss. The disease severity is highly variable and impairments may result in wheelchair boundness. No therapy is available yet. Numerous rodent models for the various CMT subtypes are available today. The selection of the correct animal model for the specific CMT subtype provides an important prerequisite for the successful translation of experimental findings in patients. Despite more than 20 years of remarkable progress in CMT research, the disease is still left untreatable. There is a growing number of experimental therapeutic strategies that may be translated into future clinical trials in patients with CMT. The slow disease progression and insensitive outcome measures hamper clinical therapy trials in CMT. Biomarkers may provide powerful tools to monitor therapeutic efficacy. Recently, we have shown that transcriptional profiling can be utilized to assess and predict the disease severity in a transgenic rat model and in affected humans.

  14. A nonantibiotic chemically modified tetracycline (CMT-3) inhibits intimal thickening.

    PubMed

    Islam, Muzharul M; Franco, Christopher D; Courtman, David W; Bendeck, Michelle P

    2003-10-01

    Recent research has shown that the tetracycline antibiotics are pluripotent drugs that inhibit the activity of matrix metalloproteinases (MMPs) and affect many cellular functions including proliferation, migration, and matrix remodeling. We have shown that doxycycline inhibits MMP activity and intimal thickening after injury of the rat carotid artery, however we do not know whether these effects are because of the antibiotic, anti-MMP, or other actions of doxycycline. Recently, chemically modified tetracyclines have been synthesized that lack antibiotic activity but retain anti-MMP activity (CMT-3), or lack both antibiotic and anti-MMP activity (CMT-5). In the current study we have assessed the effects of treatment with CMT-3 or CMT-5 on intimal thickening after balloon catheter injury of the rat carotid artery. Rats were treated by oral gavage with 15 mg/kg/day CMT-3 or CMT-5. CMT-3 significantly reduced smooth muscle cell (SMC) proliferation in both the medial and intimal layers of the injured rat carotid artery compared to CMT-5. Furthermore, CMT-3 inhibited SMC migration from the media to the intima by 86% at 4 days after injury. CMT-3 also decreased MMP-2 activity. Finally, we found that CMT-3 treatment resulted in a significant reduction in intimal cross-sectional area from 0.23 +/- 0.01 mm(2) in the CMT-5 control group to 0.19 +/- 0.01 mm(2). There was also a reduction in elastin and collagen accumulation within the intima. We conclude that CMT-3 attenuated intimal thickening after arterial injury by inhibiting SMC proliferation, migration and MMP activity, and accumulation of extracellular matrix. The inhibitory effects of CMT-3 were independent of the antibiotic properties, but were dependent on the anti-MMP activity of the tetracycline family.

  15. New mutations in CMT 1 and HNPP

    SciTech Connect

    Vandenberghe, A.; Boucherat, M.; Bonnebouche, C.

    1994-09-01

    The majority of mutations in CMT 1 (Charcot-Marie-Tooth disease type 1) are due to a duplication of a 1.5 Mb fragment from chromosome 17 containing the PMP22 myelin gene. In addition, micromutations are found in the genes for PMP22 and myelin Po. We collected data from over one hundred families with a duplication in 17p11.2. In about 10% of these families, a de novo mutation was observed. All parents were clinically examined as normal and correct paternity was confirmed. Some families were informative for polymorphic probes located in the duplicated region, and we could deduce a majority of new mutations to be from paternal origin. HNPP (hereditary neuropathy with liability to pressure palsies) is believed to be the reciprocal product of an unequal crossing over underlying the CMT 1 mutation and is due to a deletion of the 1.5 Mb fragment. One new HNPP mutation was found among 7 deleted HNPP families. This mutation is of paternal origin. Clinically assigned CMT 1 patients without a duplication are screened for micromutations applying the SSCP technique. In one family, a de novo mutation was found in the gene for Po.

  16. Analysis of the CMT1A-REP repeat: mapping crossover breakpoints in CMT1A and HNPP.

    PubMed

    Kiyosawa, H; Lensch, M W; Chance, P F

    1995-12-01

    The CMT1A-REP repeat sequence flanks a 1.5 megabase pair (Mb) segment of chromosome 17p11.2-12 which is duplicated in Charcot-Marie-Tooth neuropathy type 1A (CMT1A) and deleted in hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A-REP repeat is proposed to mediate misalignment and unequal crossover resulting in reciprocal chromosomal rearrangements in CMT1A and HNPP. We have constructed a physical map of the proximal and distal CMT1A-REP repeats. Cloned fragments from CMT1A-REP repeat regions are used to determine the size of the repeats and assess regions of homology. The crossover breakpoints were mapped in series of 30 unrelated CMT1A patients and 22 unrelated HNPP patients. The CMT1A-REP repeat spans approximately 27 kilobase pairs and appears to be continuous. Locations of restriction enzyme sites are highly conserved for the proximal and distal CMT1A-REP repeats. All crossovers mapped within the CMT1A-REP repeat sequence and heterogeneity for breakpoint location demonstrated. Seventy-seven percent (40 to 52) of CMT1A and HNPP chromosomes contained breakpoints which mapped within a 7.9 kb interval, suggesting the presence of a possible 'hotspot'for recombination in CMT1A-REP. DNA sequence analysis for 4 kb of the interval containing the majority of crossovers revealed over 98% sequence identity between proximal and distal CMT1A-REP repeat sequences. Probes useful for molecular-based diagnosis of CMT1A and HNPP are described.

  17. Audio based surveillance forcognitive assistance using a CMT microphone within socially assistive technology.

    PubMed

    Rougui, J E; Istrate, D; Souidene, W; Opitz, M; Riemann, M

    2009-01-01

    This work proposes a system for Acoustic Event Detection and Classification (AEDC) using enhanced audio signal provided by a CMT (Coincidence Microphone Technology) microphone. The CMT microphone through signal processing algorithm provides an enhanced signal in several azimuths with a step of 15 degrees . The AEC module exploits this technology to increase classification performance. The automatic detection system based on DWT uses an adaptive threshold for a different energy level and sampling rate quality. The classification system is based on an unsupervised order estimation of Gaussian mixture model adapted to the variability of sound event acoustic information and the representation cost.

  18. Two novel MPZ mutations in Chinese CMT patients.

    PubMed

    Liu, Lei; Li, Xiaobo; Zi, Xiaohong; Huang, Shunxiang; Zhan, Yajing; Jiang, Mingming; Guo, Jifeng; Xia, Kun; Tang, Beisha; Zhang, Ruxu

    2013-09-01

    To investigate the myelin protein zero (MPZ) gene mutation and related clinical features in Chinese Charcot-Marie-Tooth (CMT) patients, we screened the coding sequence of MPZ in 70 unrelated CMT index patients after excluding the PMP22 duplication, Cx32 and MFN2 mutations. We found four different missense mutations: c.194C>T, c.242A>T, c.371C>T, and c.419C>G. The frequency of MPZ mutation was approximately 4.35% of the total, 3.08% of CMT1, and 6% of CMT2. Mutations c.242A>T and c.419C>G are novel. The mutation c.242A>T exhibited late onset and rapidly progressive CMT2 phenotype. The mutation c.419C>G exhibited relatively late onset and slowly progressive CMT1 phenotype. © 2013 Peripheral Nerve Society.

  19. Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP): reliable detection of the CMT1A duplication and HNPP deletion using 8 microsatellite markers in 2 multiplex PCRs.

    PubMed

    Seeman, P; Mazanec, R; Zidar, J; Hrusáková, S; Ctvrtecková, M; Rautenstrauss, B

    2000-10-01

    Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are the most frequent inherited disorders of the peripheral nervous system. They are clinically and genetically heterogeneous. A submicroscopic tandem duplication of 1. 5 Mb in chromosome 17p11.2-12 comprising the PMP22 gene is found in 70.7% of autosomal dominant Charcot-Marie-Tooth type 1 (CMT1) patients. A reciprocal deletion is found in 87.6% of HNPP patients. The size of the typical CMT1A duplication is too small for classical cytogenetics and the whole region including the CMT1A-REP elements is sometimes too complex for a single DNA analysis method. We present results of a multiplex PCR of 8 microsatellite markers with multicolour fluorescence primer labelling followed by fragment analysis on an ABI 310 Prism analyzer to simplify the diagnostic procedure. Results for 24 patients can be obtained within 24 h. This method was applied on 92 DNA samples of unrelated patients carrying a typical CMT1A duplication previously confirmed by two colour fluorescence in situ hybridization (FISH, probe c132G8) and EcoRI/SacI Southern blotting (probe pLR7.8). Three alleles of three different sizes were clearly detected at least once in 88 of them (95.6%). Subsequently this analysis was applied on 312 Czech patients and revealed a CMT1A/HNPP rearrangement in 109 out of them.

  20. Physical and transcriptional map in the CMT 1A region

    SciTech Connect

    Chevillard, C.; Passage, E.; Cudrey, C.

    1994-09-01

    The Charcot-Marie-Tooth disease type 1A (CMT1A) has been mapped to the proximal short arm of chromosome 17. CMT1A is the most frequent of the motor and sensory peripheral neuropathies and is associated with a duplication of a 1.5 Mb fragment in proximal 17p12. Several groups have proposed that the gene coding for peripheral myelin protein-22 (PMP-22) as the candidate gene for CMT1A. We have recently published a {open_quote}MegaYAC{close_quote} contig of 6 Mb which covers the CMT1A critical region. In order to isolate new genes localized in this region, we used a {open_quote}physical trapping {close_quote} strategy derived from the direct cDNA selection technique developed by Parimoo et al. This approach has allowed us to construct cDNA {open_quotes}minilibraries{close_quotes} using YAC DNA from the CMT1A region. One of the clones in these minilibraries has been mapped back to the CMT1A duplication. Other potentially interesting clones are in the process of further characterization. Furthermore, we have mapped several Genethon microsatellites in the 6 Mb YAC contig and some are located in the CMT1A duplicated region. These highly polymorphic markers should prove useful for diagnostic testing in CMT1A.

  1. First Carlsberg Meridian Telescope (CMT) CCD Catalogue.

    NASA Astrophysics Data System (ADS)

    Bélizon, F.; Muiños, J. L.; Vallejo, M.; Evans, D. W.; Irwin, M.; Helmer, L.

    2003-11-01

    The Carlsberg Meridian Telescope (CMT) is a telescope owned by Copenhagen University Observatory (CUO). It was installed in the Spanish observatory of El Roque de los Muchachos on the island of La Palma (Canary Islands) in 1984. It is operated jointly by the CUO, the Institute of Astronomy, Cambridge (IoA) and the Real Instituto y Observatorio de la Armada of Spain (ROA) in the framework of an international agreement. From 1984 to 1998 the instrument was provided with a moving slit micrometer and with its observations a series of 11 catalogues were published, `Carlsberg Meridian Catalogue La Palma (CMC No 1-11)'. Since 1997, the telescope has been controlled remotely via Internet. The three institutions share this remote control in periods of approximately three months. In 1998, the CMT was upgraded by installing as sensor, a commercial Spectrasource CCD camera as a test of the possibility of performing meridian transits observed in drift-scan mode. Once this was shown possible, in 1999, a second model of CCD camera, built in the CUO workshop with a better performance, was installed. The Spectrasource camera was loaned to ROA by CUO and is now installed in the San Fernando Automatic Meridian Circle in San Juan (CMASF). In 1999, the observations were started of a sky survey from -3deg to +30deg in declination. In July 2002, a first release of the survey was published, with the positions of the observed stars in the band between -3deg and +3deg in declination. This oral communication will present this first release of the survey.

  2. Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations.

    PubMed

    Yang, Xiaomin; Zhao, Lin; Almasy, Laszlo; Garamus, Vasil M; Zou, Aihua; Willumeit, Regine; Fan, Saijun

    2013-06-25

    Chemically modified tetracyclines (CMTs) have been reported to strongly inhibit proliferation and metastasis of various cancers, but their efficacy is restricted by poor water solubility. In the present study, a hydrophilic 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) was produced by high pressure homogenization (HPH). The physical properties of CMT-3/NLC formulations were characterized by dynamic light scattering (DLS), high efficiency liquid chromatography (HPLC), atomic force microscopy (AFM), scanning electron microscopy (SEM), small-angle neutron scattering (SANS), small-angle X-ray scattering (SAXS) and wide-angle X-ray powder diffraction (XRD). The lipid and surfactant ingredients, as well as drug/lipid concentrations (m/m) were optimized to produce stable and sustained NLC formulations. In vitro cytotoxicity of CMT-3/NLC against HeLa cells was evaluated by MTT assay. The diameter of CMT-3/NLC was found to increase from 153.1±3.0 nm to a maximum of 168.5±2.0 nm after 30 days of storage, while the entrapment efficiency remained constant at >90%. CMT-3/NLC demonstrated a burst-sustained release profile in release media with different pH, a property attributed to the 3-dimensional structure of CMT-3/NLC. Cell uptake and localization studies indicated that NLC reached the cytoplasm and could thereby facilitate CMT-3 entry into HeLa cells.

  3. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMT1A duplication

    SciTech Connect

    Wise, C.A.; Davis, S.N.; Heju, Z.; Pentao, L.; Patel, P.I.; Lupski, J.R. ); Garcia, C.A. )

    1993-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A DNA duplication. Three methodologies were used to assess the duplication: Measurement of dosage differences between RFLP alleles, analysis of polymorphic (GT)[sub n] repeats, and detection of a junction fragment by pulsed-field gel electrophoresis. The CMT1A duplication was found in 68% of the 63 unrelated CMT patients with electrophysiological studies consistent with CMT type 1 (CMT1). The CMT1A duplication was detected as a de novo event in two CMT1 families. Twelve CMT patients who did not have decreased nerve conduction velocities consistent with a diagnosis of CMT type 2 (CMT2) were found not to have the CMT1A duplication. The most informative molecular method was the detection of the CMT1A duplication-specific junction fragment. Given the high frequency of the CMT1A duplication in CMT patients and the high frequency of new mutations, the authors conclude that a molecular test for the CMT1A DNA duplication is very useful in the differential diagnosis of patients with peripheral neuropathies. 61 refs., 4 figs.

  4. Underestimated associated features in CMT neuropathies: clinical indicators for the causative gene?

    PubMed

    Werheid, Friederike; Azzedine, Hamid; Zwerenz, Eva; Bozkurt, Ahmet; Moeller, Marcus J; Lin, Lilian; Mull, Michael; Häusler, Martin; Schulz, Jörg B; Weis, Joachim; Claeys, Kristl G

    2016-04-01

    Charcot-Marie-Tooth neuropathy (CMT) is a genetically heterogeneous group of peripheral neuropathies. In addition to the classical clinical phenotype, additional features can occur. We studied a wide range of additional features in a cohort of 49 genetically confirmed CMT patients and performed a systematic literature revision. Patients harbored a PMP22 gene alteration (n = 28) or a mutation in MPZ (n = 11), GJB1 (n = 4), LITAF (n = 2), MFN2 (n = 2), INF2 (n = 1), NEFL (n = 1). We identified four novel mutations (3 MPZ, 1 GJB1). A total of 88% presented at least one additional feature. In MPZ patients, we detected hypertrophic nerve roots in 3/4 cases that underwent spinal MRI, and pupillary abnormalities in 27%. In our cohort, restless legs syndrome (RLS) was present in 18%. We describe for the first time RLS associated with LITAF or MFN2 and predominant upper limb involvement with LITAF. Cold-induced hand cramps occurred in 10% (PMP22,MPZ,MFN2), and autonomous nervous system involvement in 18% (PMP22,MPZ, LITAF,MFN2). RLS and respiratory insufficiency were mostly associated with severe neuropathy, and pupillary abnormalities with mild to moderate neuropathy. In CMT patients, additional features occur frequently. Some of them might be helpful in orienting genetic diagnosis. Our data broaden the clinical spectrum and genotype-phenotype associations with CMT.

  5. Molecular basis of axonal dysfunction and traffic impairments in CMT.

    PubMed

    Gentil, Benoit J; Cooper, Laura

    2012-08-01

    Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders. It comprises a group of diseases caused by mutations in genes involved in Schwann cells homeostasis and neuronal function that affect the peripheral nerves. So far mutations in more than 33 genes have been identified causing either the demyelinating form (CMT1) or the axonal form (CMT2). Genes involving a large variety of unrelated functions may lead to the same phenotype when mutated. Our review will focus on the common link between genes causing axonal phenotypes like MFN2, KIF1B, DYNC1H1, Rab7, TRPV4, ARSs, NEFL, HSPB1, MPZ, and HSPB8. While KIF1B and DYNC1H1, two genes coding for molecular motors, are directly linked to axonal transport, the involvement of the other CMT2-causing genes in this function is less obvious. However, the last years have seen a growing list of evidence demonstrating that intracellular trafficking and mitochondrial dynamics might be dysfunctional in CMT2, and these mechanisms might present a common link between dissimilar CMT2-causing genes. The involvement of impaired transport in the pathogenesis of other rare neurological diseases or recessive CMT2 is also discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. CMT4D (NDRG1 mutation): genotype-phenotype correlations.

    PubMed

    Ricard, Emilie; Mathis, Stéphane; Magdelaine, Corinne; Delisle, Marie-Bernadette; Magy, Laurent; Funalot, Benoît; Vallat, Jean-Michel

    2013-09-01

    Charcot-Marie-Tooth (CMT) disease is a heterogeneous condition with a large number of clinical, electrophysiological and pathological phenotypes. More than 40 genes are involved. We report a child of gypsy origin with an autosomal recessive demyelinating phenotype. Clinical data, familial history, and electrophysiological studies were in favor of a CMT4 sub-type. The characteristic N-Myc downstream-regulated gene 1 (NDRG1) mutation responsible for this CMT4D phenotype was confirmed: p.R148X. The exact molecular function of the NDRG1 protein has yet to be elucidated.

  7. CMT Welding of Low Carbon Steel Thin Sheets

    NASA Astrophysics Data System (ADS)

    Stanciu, E. M.; Pascu, A.; Gheorghiu, I.

    2017-06-01

    This paper addresses to the cold metal transfer MAG welding of low carbon steel thin sheets. The paper highlights the advantages of using CMT process for but joining of S235 carbon sheets by comparing the CMT with the conventional synergic pulse MAG welding. A lower weld bead area and heat affected zone is obtained by the continuous movement of the wire, digitally synchronised with the short-circuit of the arc. CMT welding can produce good welds even in unfavorable conditions, such as using thin plates and high diameter wire.

  8. Unfolded protein response, treatment and CMT1B

    PubMed Central

    Bai, Yunhong; Patzko, Agnes; Shy, Michael E.

    2013-01-01

    CMT1B is the second most frequent autosomal dominant inherited neuropathy and is caused by assorted mutations of the myelin protein zero (MPZ) gene. MPZ mutations cause neuropathy gain of function mechanisms that are largely independent MPZs normal role of mediating myelin compaction. Whether there are only a few or multiple pathogenic mechanisms that cause CMT1B is unknown. Arg98Cys and Ser63Del MPZ are two CMT1B causing mutations that have been shown to cause neuropathy in mice at least in part by activating the unfolded protein response (UPR). We have recently treated Arg98Cys mice with derivatives of curcumin that improved the neuropathy and reduced UPR activation.1 Future studies will address whether manipulating the UPR will be a common or rare strategy for treating CMT1B or other forms of inherited neuropathies. PMID:25002989

  9. A Family Harboring CMT1A Duplication and HNPP Deletion.

    PubMed

    Lee, Jung Hwa; Kang, Hee Jin; Song, Hyunseok; Hwang, Su Jin; Cho, Sun-Young; Kim, Sang-Beom; Kim, Joonki; Chung, Ki Wha; Choi, Byung-Ok

    2007-06-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with duplication of chromosome 17p11.2-p12, whereas hereditary neuropathy with liability to pressure palsies (HNPP), which is an autosomal dominant neuropathy showing characteristics of recurrent pressure palsies, is associated with 17p11.2-p12 deletion. An altered gene dosage of PMP22 is believed to the main cause underlying the CMT1A and HNPP phenotypes. Although CMT1A and HNPP are associated with the same locus, there has been no report of these two mutations within a single family. We report a rare family harboring CMT1A duplication and HNPP deletion.

  10. A review of genetic counseling for Charcot Marie Tooth disease (CMT).

    PubMed

    Siskind, Carly E; Panchal, Seema; Smith, Corrine O; Feely, Shawna M E; Dalton, Joline C; Schindler, Alice B; Krajewski, Karen M

    2013-08-01

    Charcot Marie Tooth disease (CMT) encompasses the inherited peripheral neuropathies. While four genes have been found to cause over 90 % of genetically identifiable causes of CMT (PMP22, GJB1, MPZ, MFN2), at least 51 genes and loci have been found to cause CMT when mutated, creating difficulties for clinicians to find a genetic subtype for families. Here, the classic features of CMT as well as characteristic features of the most common subtypes of CMT are described, as well as methods for narrowing down the possible subtypes. Psychosocial concerns particular to the CMT population are identified. This is the most inclusive publication for CMT-specific genetic counseling.

  11. Biodistribution of radiolabeled [(3)H] CMT-3 in rats.

    PubMed

    Chen, J; Bookbinder, M; Ryan, M E; Golub, L M; Ashley, R; Ramamurthy, N S

    2001-02-01

    CMT-3 is a NON-ANTIMICROBIAL tetracycline (TC), chemically modified to enhance its collagenase-inhibitory property. This property is therapeutically useful in treating diseases such as periodontitis, cancer and arthritis. CMT-3 was labeled with tritium [(3)H] at Carbon 7. Four adult male Sprague-Dawley rats (350--400 g body weight) were gavaged once with a mixture of cold CMT-3 and [(3)H] CMT-3 (750 microCi). An additional four rats were gavaged for 2 days with cold CMT-3(15 mg/Kg/day) and on the third day the rats were gavaged with a mixture of cold and [(2)H] CMT-3 (750 microCi); and all 8 rats were placed in the metabolic cages. Blood samples were collected from the tail at multiple intervals from 1--14 hr after [(3)H] CMT-3 administration. At 14 hr, the rats were anesthetized, euthanized and various tissues including visceral organs were removed and weighed. The contents of GI tracts were emptied and added to the fecal pellets and weighed. The urine samples were collected and volume measured. Each tissue or organ was minced finely with scissors and 100 mg of tissue was digested in 1 ml of Tissue-solv (Packard Lab), for 4 hrs at 37 degrees C and each sample was diluted up to 10 ml of distilled water. A 100 microl aliquot was taken and diluted with an equal volume of glacial acetic acid, 10 ml of Atom-lite was added and counted for radioactivity in a liquid scintillation spectrometer. This biodistribution study revealed that over 14 hrs, 54% and 3% of [(3)H] CMT-3 were excreted in the feces and urine, respectively. The serum [(3)H] CMT-3 count reached its maximum value at about 12 hours. The tissues retained the CMTs as follow: muscle (23%); skin (2.41%); bone (1.72%); and the brain retained 0.21% of the label. The radioactive CMT-3 in the visceral organs is as follows: GI tract - its contents (8.9%); heart (0.41%), testis (0.41%); lungs >(0.16%); spleen (0.08%); liver (0.03%); kidneys > (0.02%).

  12. Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A.

    PubMed

    Kumar, Chundi Vinay; Swetha, Rayapadi G; Anbarasu, Anand; Ramaiah, Sudha

    2014-01-01

    The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures.

  13. The comparison of maintenance treatment with capecitabine (CMT) and non-maintenance treatment with capecitabine (non-CMT) in patients with metastatic breast cancer.

    PubMed

    Dong, Guolei; Jia, Yan; Wang, Xiaorui; Li, Shufen; Wang, Chen; Shi, Yehui; Tong, Zhongsheng

    2015-01-01

    The study examined the response rate, response duration and toxicity of maintenance treatment (CMT) and non-maintenance treatment with capecitabine (non-CMT) in metastatic breast cancer (MBC). Between September 2009 and July 2013, a group of 82 patients with MBC, who had progressed after anthracycline/taxane chemotherapy, was treated with a capecitabine-based chemotherapy and divided into two groups. 54 patients received CMT 1.5 g twice a day from days 1 to 14, and 28 patients achieved non-CMT. Treatment was continued until disease progression or unacceptable toxicity. The median age of patients treated with CMT and non-CMT was 57 years (range 38-78) and 50 years (range 37-77). The evaluation of treatment effect was possible in all patients. The overall response rate (ORR) was 29.7% (16 cases), including 3 (5.6%) complete responses (CR) and 13 (24.1%) partial responses (PR). Stable disease (SD) was observed in 7.4% of patients receiving CMT (54 patients). In the group receiving non-CMT, ORR was 3.6% (1 case). The median PFS in CMT group was 36 weeks, while in non-CMT group was 24 weeks. The most common adverse event was hematologic toxicity (74.1%), with the incidence of grade 1-2/3-4 was 70.4% and 3.7%. Hand-foot syndrome was the most frequent non-hematologic form of toxicity, occurring in 70.4% of cases. There were no treatment-related deaths. CMT is an effective and safe treatment for pretreated metastatic breast cancer patients. And CMT appears to be a more efficacious treatment than non-CMT.

  14. Visualizing the Complexities of Instruction: The CMT Paradigm.

    ERIC Educational Resources Information Center

    Branch, Robert C.

    The relationship between instruction and instructional design is explored. The aim of instruction is to assist the individual as learner. The Learner, the Content, the Media, the Teacher Function, and the Context within which learning is to occur interact during a period of time to form an instructional episode (the CMT paradigm). Considering all…

  15. [Charcot-Marie-Tooth (CMT) disease: an update].

    PubMed

    Vallat, Jean-Michel; Funalot, Benoît

    2010-10-01

    Charcot-Marie-Tooth (CMT) is the generic name given to a group of genetic disorders characterized by a relatively isolated dysfunction of peripheral nerves, with combined motor and sensory impairment. These CMT syndromes are the most frequent genetically-determined peripheral neuropathies, with a global prevalence between 4.7 and 36/100,000. Their clinical phenotype is predominantly motor, with a grossly symmetrical distal amyotrophy involving both lower and upper limbs. Mode of inheritance is variable: autosomal dominant, autosomal recessive or X-linked. Apparently sporadic forms can be a difficult diagnosis and they must be considered in all patients with a chronic polyneuropathy which is not clearly of acquired origin. During the last two decades, the identification of more than 25 genes mutated in CMT syndromes has complicated the classification of these disorders. Knowledge of the function of some of these genes has improved our understanding of the pathogenesis of myelinic or axonal dysfunction in CMT, but for some others their function remains elusive or unknown.

  16. Pain assessment in Charcot-Marie-Tooth (CMT) disease.

    PubMed

    Ribiere, C; Bernardin, M; Sacconi, S; Delmont, E; Fournier-Mehouas, M; Rauscent, H; Benchortane, M; Staccini, P; Lantéri-Minet, M; Desnuelle, C

    2012-04-01

    The objective of our study was to describe and evaluate the prevalence of chronic pain in persons with Charcot-Marie-Tooth (CMT) disease during a multidisciplinary consultation at the Center of Reference for Neuromuscular Diseases. This prospective study was conducted between 2008 and 2010, it was a partnership between a Center of Reference for Neuromuscular Diseases (Centre de référence des maladies neuromusculaires [CRMD]) and a Department for the Assessment and Treatment of Pain (Département d'évaluation et de traitement de la douleur [DETD]). The evaluation consisted in a complete assessment of each patient during the first multidisciplinary consultation, with a previously established diagnosis validated by genetic testing, by various specialists: neurologist, PM&R physician, pain management specialist and physiotherapist. The evaluation tools used were Visual Analogical Scale (VAS), Hospital Anxiety and Depression Scale (HAD), DN4 scale, Neuropathic Pain Symptom Inventory (NPSI) (if DN4≥4), Pain Questionnaire of Saint Antoine (QDSA) (if DN4<4), body representation to define the painful areas, Overall Neuropathy Limitations Scale (ONLS), Medical Research Council scale (MRC), Short Questionnaire on Pain (QCD), VAS during transfers, self-care, getting dressed and physiotherapy sessions and quantified use of analgesics. A total of 50 patients were included (28 women, 22 men); two patients (one man and one woman) were discarded from the study because of missing pain assessment data. Mean age was 47years (R: 14-85), in average the symptoms had been present for the past 20years (R: 0.3-68), most patients had little impairment, the mean MRC was 53 (R: 36-60), with CMT1A being predominant (CMT1A: 76.9%, CMTX: 13.5%, CMT2: 5.8%, CMT4: 3.8%). It is noted that 65.4% of patients reported some pain with a mean duration of pain at 140months (R: 5-660). The mean VAS was 5.5 (R: 1-10), greater than 4 in 79.4% of cases, requiring the use of analgesics in 38.4% of cases

  17. CMT-3 inhibits orthodontic tooth displacement in the rat.

    PubMed

    Bildt, M M; Henneman, S; Maltha, J C; Kuijpers-Jagtman, A M; Von den Hoff, J W

    2007-06-01

    Orthodontic tooth movement requires extensive remodeling of the periodontal ligament (PDL) and the alveolar bone. Osteoclasts resorb bone, allowing teeth to migrate in the direction of the force. Matrix metalloproteinases (MMPs) are able to degrade the extracellular matrix of the periodontal tissues. Chemically modified tetracyclines (CMTs) can inhibit MMPs, but lack antimicrobial activity. We hypothesize that CMT-3 will decrease the rate of orthodontic tooth movement in the rat. Eighteen Wistar rats received a standardized orthodontic appliance at one side of the maxilla. During 14 days, three groups of six rats received a daily dose of 0, 6 or 30mg/kg CMT-3, and tooth displacement was measured. Thereafter, osteoclasts were counted on histological sections using an ED-1 staining. Multi- and mononuclear ED-1-positive cells in the PDL were also counted. In addition, sections were stained for MMP-9. CMT-3 significantly inhibited tooth movement (p=0.03) and also decreased the number of osteoclasts at the compression sides in the 30mg/kg group (p<0.05). Significantly more mono- than multinuclear ED-1-positive cells were present in the PDL, but no significant differences were found between the dosage groups. Osteoclasts in the 30mg/kg group seemed to contain less MMP-9 than in the control. CMT-3 inhibits tooth movement in the rat, probably by reducing the number of osteoclasts at the compression side. This might be due to induction of apoptosis in activated osteoclasts or reduced osteoclast migration. Reduced MMP activity by CMT-3 might also directly inhibit degradation of the organic bone matrix.

  18. Phenotypes and cellular effects of GJB1 mutations causing CMT1X in a cohort of 226 Chinese CMT families.

    PubMed

    Liu, L; Li, X B; Hu, Z H M; Zi, X H; Zhao, X; Xie, Y Z; Huang, S H X; Xia, K; Tang, B S; Zhang, R X

    2017-06-01

    The aim of this study is to explore the phenotypic and genotypic features of X-linked Charcot-Marie-Tooth (CMT) disease in the mainland of China and to study the cellular effects of six novel Gap junction protein beta-1 variants. We identified 25 missense and 1 non-sense mutations of GJB1 in 31 unrelated families out of 226 CMT families. The frequency of GJB1 mutations was 13.7% of the total and 65% of intermediate CMT. Six novel GJB1 variants (c.5A>G, c.8G>A, c.242T>C, c.269T>C, c.317T>C and c.434T>G) were detected in six unrelated intermediate CMT families. Fluorescence revealed that HeLa cells transfected with EGFP-GJB1-V74M, EGFP-GJB1-L81P or EGFP-GJB1-L90P had diffuse endoplasmic reticulum staining, HeLa cells transfected with EGFP-GJB1-L106P had diffuse intracellular staining, and HeLa cells transfected with EGFP-GJB1-N2S had cytoplasmic and nuclear staining. The distribution of Cx32 in HeLa cells transfected with EGFP-GJB1-F145C was similar to that of those transfected with wild-type (WT). These six variants resulted in a higher percentage of apoptosis than did WT as detected by flow cytometry and Hoechst staining. In conclusion, mutation screening should be first performed in intermediate CMT patients, especially those with additional features. The novel GJB1 variants c.5A>G, c.8G>A, c.242T>C and c.269T>C are considered pathogenic, and c.317T>C and c.434T>G are classified as probably pathogenic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Gene conversion homogenizes the CMT1A paralogous repeats.

    PubMed

    Hurles, M E

    2001-01-01

    Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Here, a statistical test to detect gene conversion between pairs of non-coding sequences is presented. It is shown that the 24 kb Charcot-Marie-Tooth type 1A paralogous repeats (CMT1A-REPs) exhibit the imprint of gene conversion processes whilst control orthologous sequences do not. In addition, Monte Carlo simulations of the evolutionary divergence of the CMT1A-REPs, incorporating two alternative models for gene conversion, generate repeats that are statistically indistinguishable from the observed repeats. Bounds are placed on the rate of these conversion processes, with central values of 1.3 x 10(-4) and 5.1 x 10(-5) per generation for the alternative models. This evidence presented here suggests that gene conversion may have played an important role in the evolution of the CMT1A-REP paralogous repeats. The rates of these processes are such that it is probable that homogenized CMT1A-REPs are polymorphic within modern populations. Gene conversion processes are similarly likely to play an important role in the evolution of other segmental duplications and may influence the rate of non-allelic homologous recombination between them.

  20. Gene conversion homogenizes the CMT1A paralogous repeats

    PubMed Central

    Hurles, Matthew E

    2001-01-01

    Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect gene conversion between pairs of non-coding sequences is presented. It is shown that the 24 kb Charcot-Marie-Tooth type 1A paralogous repeats (CMT1A-REPs) exhibit the imprint of gene conversion processes whilst control orthologous sequences do not. In addition, Monte Carlo simulations of the evolutionary divergence of the CMT1A-REPs, incorporating two alternative models for gene conversion, generate repeats that are statistically indistinguishable from the observed repeats. Bounds are placed on the rate of these conversion processes, with central values of 1.3 × 10-4 and 5.1 × 10-5 per generation for the alternative models. Conclusions This evidence presented here suggests that gene conversion may have played an important role in the evolution of the CMT1A-REP paralogous repeats. The rates of these processes are such that it is probable that homogenized CMT1A-REPs are polymorphic within modern populations. Gene conversion processes are similarly likely to play an important role in the evolution of other segmental duplications and may influence the rate of non-allelic homologous recombination between them. PMID:11801183

  1. CMT for biomedical and other applications

    SciTech Connect

    Spanne, P.

    1997-02-01

    This session includes two presentations describing applications for x-ray tomography using synchrotron radiation for biomedical uses and fluid flow modeling, and outlines advantages for using monoenergetic x-rays. Contrast mechanisms are briefly described and several graphs of absorbed doses and scattering of x-rays are included. Also presented are schematic diagrams of computerized tomographic instrumentation with camera head. A brief description of goals for a real time tomographic system and expected improvements to the system are described. Color photomicrographs of the Berea Sandstone and human bone are provided, as well as a 3-D microtomographic reconstruction of a human vertebra sample.

  2. CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer.

    PubMed

    Lee, H M; Golub, L M; Cao, J; Teronen, O; Laitinen, M; Salo, T; Zucker, S; Sorsa, T

    2001-02-01

    Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and activating pro-MMP-2, a pathway believed to mediate cancer induced tissue breakdown. CMT-3 (6-demethyl, 6-deoxy, 4-dedimethylamino TC) has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture and to inhibit tumor growth and metastasis in vivo and was used in the current in vitro study. Confluent MT1-MMP transfected COS-1 cells were harvested, washed thoroughly, subjected to N(2) cavitation and cell membrane enriched fractions were isolated by sequential centrifugations. This MT1-MMP preparation exhibited (i) pro-MMP-2 activating activity as shown by molecular weight shift of this gelatinase from 72 kDa to 62 kDa using gelatin zymography, and (ii) the ability to degrade both [(3)H-methyl] gelatin and casein at 37 degrees C. Adding CMT-3 at final concentrations of 5--20microM inhibited MT1-MMP gelatinolytic and caseinolytic activity, blocked MT1-MMP activation of pro-MMP-2, and decreased invasiveness (using the Matrigel system) of HT-1080 fibrosarcoma cells. The inhibition of MT1-MMP by CMT-3 may partially explain the inhibition of cancer cell -mediated tissue breakdown and invasiveness by this non-antimicrobial tetracycline analog.

  3. Immortalization and characterization of a new canine mammary tumour cell line FR37-CMT.

    PubMed

    Raposo, L R; Roma-Rodrigues, C; Faísca, P; Alves, M; Henriques, J; Carvalheiro, M C; Corvo, M L; Baptista, P V; Pombeiro, A J; Fernandes, A R

    2017-09-01

    Here we describe the establishment of a new canine mammary tumour (CMT) cell line, FR37-CMT that does not show dependence on female hormonal signaling to induce tumour xenografts in NOD-SCID mice. FR37-CMT cell line has a stellate or fusiform shape, displays the ability to reorganize the collagen matrix, expresses vimentin, CD44 and shows the loss of E-cadherin which is considered a fundamental event in epithelial to mesenchymal transition (EMT). The up-regulation of ZEB1, the detection of phosphorylated ERK1/2 and the downregulation of DICER1 and miR-200c are also in accordance with the mesenchymal characteristics of FR37-CMT cell line. FR37-CMT shows a higher resistance to cisplatin (IC50 >50 µM) and to doxorubicin (IC50 >5.3 µM) compared with other CMT cell lines. These results support the use of FR37-CMT as a new CMT model that may assist the understanding of the molecular mechanisms underlying EMT, CMT drug resistance, fostering the development of novel therapies targeting CMT. © 2016 John Wiley & Sons Ltd.

  4. A single CMT methyltransferase homolog is involved in CHG DNA methylation and development of Physcomitrella patens.

    PubMed

    Noy-Malka, Chen; Yaari, Rafael; Itzhaki, Rachel; Mosquna, Assaf; Auerbach Gershovitz, Nitzan; Katz, Aviva; Ohad, Nir

    2014-04-01

    C-5 DNA methylation is an essential mechanism controlling gene expression and developmental programs in a variety of organisms. Though the role of DNA methylation has been intensively studied in mammals and Arabidopsis, little is known about the evolution of this mechanism. The chromomethylase (CMT) methyltransferase family is unique to plants and was found to be involved in DNA methylation in Arabidopsis, maize and tobacco. The moss Physcomitrella patens, a model for early terrestrial plants, harbors a single homolog of the CMT protein family designated as PpCMT. Our phylogenetic analysis suggested that the CMT family is unique to embryophytes and its earliest known member PpCMT belongs to the CMT3 subfamily. Thus, P. patens may serve as a model to study the ancient functions of the CMT3 family. We have generated a ΔPpcmt deletion mutant which demonstrated that PpCMT is essential for P. patens protonema and gametophore development and is involved in CHG methylation as demonstrated at four distinct genomic loci. PpCMT protein accumulation pattern correlated with proliferating cells and was sub-localized to the nucleus as predicted from its function. Taken together, our results suggested that CHG DNA methylation mediated by CMT has been employed early in land plant evolution to control developmental programs during both the vegetative and reproductive haploid phases along the plant life cycle.

  5. [Evaluation of the California mastitis test (CMT) reaction in goat milk and its interpretation].

    PubMed

    Winter, P; Baumgartner, W

    1999-01-01

    For evaluation of different factors regarding CMT results 65 goats were used. Age, milking hygiene and technique of the animals were recorded and the CMT results were evaluated in relation to those parameters. Correlations between CMT results and age as well milking hygiene and -technique respectively were found. Furtheron the CMT was evaluated as indicator for mastitis diagnosis. Therefore clinical examination of the udder, bacteriological examination of milk samples (aseptically collected) and the determination of the somatic cell count were carried out. The results showed that CMT is not specific for infected udder halves. As important udder pathogens staphylococci were found, S. aureus and CNS at the same level. This investigation has shown that CMT can be used as additional diagnostic tool concerning goat mastitis, but it should not be overestimated because of different factors which influence the cell count. For the control of udder health additional diagnostic measures are of utmost necessity.

  6. Dominant GDAP1 mutations cause predominantly mild CMT phenotypes.

    PubMed

    Zimoń, M; Baets, J; Fabrizi, G M; Jaakkola, E; Kabzińska, D; Pilch, J; Schindler, A B; Cornblath, D R; Fischbeck, K H; Auer-Grumbach, M; Guelly, C; Huber, N; De Vriendt, E; Timmerman, V; Suter, U; Hausmanowa-Petrusewicz, I; Niemann, A; Kochański, A; De Jonghe, P; Jordanova, A

    2011-08-09

    Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). We aimed to investigate the frequency of disease-causing heterozygous GDAP1 mutations in ADCMT and their associated phenotype. We performed mutation analysis in a large cohort of ADCMT patients by means of bidirectional sequencing of coding regions and exon-intron boundaries of GDAP1. Intragenic GDAP1 deletions were excluded using an allele quantification assay. We confirmed the pathogenic character of one sequence variant by in vitro experiments assaying mitochondrial morphology and function. In 8 Charcot-Marie-Tooth disease (CMT) families we identified 4 pathogenic heterozygous GDAP1 mutations, 3 of which are novel. Three of the mutations displayed reduced disease penetrance. Disease onset in the affected individuals was variable, ranging from early childhood to adulthood. Disease progression was slow in most patients and overall severity milder than typically seen in autosomal recessive GDAP1 mutations. Electrophysiologic changes are heterogeneous but compatible with axonal neuropathy in the majority of patients. With this study, we broaden the phenotypic and genetic spectrum of autosomal dominant GDAP1-associated neuropathies. We show that patients with dominant GDAP1 mutations may display clear axonal CMT, but may also have only minimal clinical and electrophysiologic abnormalities. We demonstrate that cell-based functional assays can be reliably used to test the pathogenicity of unknown variants. We discuss the implications of phenotypic variability and the reduced penetrance of autosomal dominant GDAP1 mutations for CMT diagnostic testing and counseling.

  7. Locations of crossover breakpoints within the CMT1A-REP repeat in Japanese patients with CMT1A and HNPP.

    PubMed

    Yamamoto, M; Yasuda, T; Hayasaka, K; Ohnishi, A; Yoshikawa, H; Yanagihara, T; Ikegami, T; Yamamoto, T; Ohashi, H; Nishimura, T; Mitsuma, T; Kiyosawa, H; Chance, P F; Sobue, G

    1997-02-01

    The crossover breakpoints for Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are located in the CMT1A-REP repeat flanking a 1.5-Mb region of chromosome 17p11.2-12. The precise locations of the breakpoints are heterogeneous, and we analyzed the relative frequency distribution of breakpoints in 33 unrelated Japanese CMT1A and 3 unrelated HNPP families. The CMT1A-REP repeat region was divided into five regions, A, B, C, D and E, based on restriction site differences between the proximal and distal CMT1A-REP repeats. The frequency distribution of breakpoints within the CMT1A-REP repeat in the Japanese patients was 3% in region A, .78% in B/C and 19% in D, which is similar to that in Caucasian patients. This result also indicates that an 8-kb region defined by region B/C is a recombinational hotspot within the CMT1A-REP repeat in Japanese patients.

  8. Assessing CMT cell line stability by two dimensional polyacrylamide gel electrophoresis and mass spectrometry based proteome analysis.

    PubMed

    Zhang, Kelan; Wrzesinski, Krzysztof; Fey, Stephen J; Mose Larsen, Peter; Zhang, Xumin; Roepstorff, Peter

    2008-07-21

    Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by mass spectrometric identification of the proteins in the protein spots has become a central tool in proteomics. CMT167(H), CMT64(M) and CMT170(L) cell lines, selected from a spontaneous mouse lung adenocarcinoma, with high-, middle- or low-metastatic potential have been characterized in vivo. In this study, the comprehensive protein expression profiles of the CMT cell lines were analyzed at passages 5, 15 and 35 in order to assess the cell line stability. During the passages 5 to 15, the expression profiles of CMT cells remained reasonably stable as evidenced by only 0.7%, 3.9% and 1.1% proteins changed in CMT167(H), CMT64(M) and CMT170(L) respectively. However, the number of differentially expressed proteins were considerably increased at passage 35 in CMT64(M) and CMT170(L) while CMT167(H) remained stable. Based on our selection criteria, 22, 109 and 84 spots in CMT167(H), CMT64(M) and CMT170(L) were selected for protein identification by MS and 99 unique proteins were identified. Bioinformatics analysis indicated that most of these proteins participate in cellular metabolism. In conclusion, proteomics was found to be a useful tool for assessing differences in cell line stability. This approach provided a tool to select the best cell line and optimal subculture period for studies of cancer related phenomena and for testing the effect of potential anticancer drugs.

  9. A novel GDAP1 mutation 439delA is associated with autosomal recessive CMT disease.

    PubMed

    Georgiou, Domna-Maria; Nicolaou, Paschalis; Chitayat, David; Koutsou, Pantelitsa; Babul-Hirji, Riyana; Vajsar, Jiri; Murphy, Jillian; Christodoulou, Kyproula

    2006-08-01

    Charcot-Marie-Tooth (CMT) disease is the most common form of inherited motor and sensory neuropathy. Based on neurophysiological and neuropathological criteria CMT has been sub-classified into two main types: demyelinating and axonal. Furthermore, it is genetically heterogeneous with autosomal dominant, autosomal recessive (AR) and X-linked modes of inheritance. Thus far, seven genes have been identified in association with the demyelinating AR-CMT disease. We hereby report our clinical and molecular genetic findings in a consanguineous family with AR-CMT. Two young sisters with AR-CMT and other non-affected family members were clinically and electrophysiologically evaluated and then molecular genetic investigation was carried out in order to identify the pathogenic mutation. Following an initial indication for linkage of the family to the CMT4A locus on chromosome 8, we sequenced the Ganglioside-induced differentiation-associated protein 1 (GDAP1) gene and identified a single nucleotide deletion in exon 3 that is associated with AR-CMT in the family. We identified a novel GDAP1 439delA mutation that is associated with AR-CMT in a consanguineous family of Iranian descent with two affected young girls and a history in other members of the family.

  10. Automated and Rapid Determinations of Earthquake Source Parameters in Indonesia: Comparisons with Global CMT Solutions

    NASA Astrophysics Data System (ADS)

    Nakano, M.; Yamashina, T.; Kumagai, H.; Inoue, H.; S.; F.

    2008-12-01

    receiving initial hypocenter information from the GEOFON email alert. Using the displacement seismograms with a total length of 512 s and Green's functions stored in a library, the inversion is performed to estimate the source parameters. Finally, when the result is judged sufficiently accurate, the estimated source parameters are displayed on our web server (http://www.isn.bosai.go.jp/en/index.html). Using the inversion method, we created a CMT catalogue for earthquakes in Indonesia that occurred between July 2006 and May 2008. We obtained CMT solutions for 180 earthquakes with the moment magnitude larger than 5. We compared the source parameters with those obtained by the GCMT project. The average differences in the horizontal source location and depth are 40.7 km and -5.6 km, respectively. The horizontal difference corresponds to twice the grid spacing of the grid search. The moment magnitudes obtained by our method are almost identical to those estimated by the GCMT project. These results indicate that our CMT solutions are consistent with those obtained by the GCMT project. The average time required for the source parameter estimations by this system is 13 minutes after the occurrence of earthquakes, which is much shorter than that required for CMT estimations based on global seismic networks. Seismic monitoring based on our inversion system provides early notification of detailed characterizations of earthquakes including the moment function, which may be useful for identification of tsunami earthquakes and can provide supporting information for tsunami warnings.

  11. CHANNEL MORPHOLOGY TOOL (CMT): A GIS-BASED AUTOMATED EXTRACTION MODEL FOR CHANNEL GEOMETRY

    SciTech Connect

    JUDI, DAVID; KALYANAPU, ALFRED; MCPHERSON, TIMOTHY; BERSCHEID, ALAN

    2007-01-17

    This paper describes an automated Channel Morphology Tool (CMT) developed in ArcGIS 9.1 environment. The CMT creates cross-sections along a stream centerline and uses a digital elevation model (DEM) to create station points with elevations along each of the cross-sections. The generated cross-sections may then be exported into a hydraulic model. Along with the rapid cross-section generation the CMT also eliminates any cross-section overlaps that might occur due to the sinuosity of the channels using the Cross-section Overlap Correction Algorithm (COCoA). The CMT was tested by extracting cross-sections from a 5-m DEM for a 50-km channel length in Houston, Texas. The extracted cross-sections were compared directly with surveyed cross-sections in terms of the cross-section area. Results indicated that the CMT-generated cross-sections satisfactorily matched the surveyed data.

  12. Genetic and physical mapping of the genomic region spanning CMT4A

    SciTech Connect

    Othmane, K.B.; Loeb, D.; Roses, A.D.

    1994-09-01

    Autosomal recessive Charcot-Marie-Tooth disease (CMT4) is a severe childhood neuropathy classified into three types: A, B, and C. We previously mapped CMT4A to chromosome 8q13-q21 in four large Tunisian families. Analysis of recombination events suggested the order: cent.-D8S279-(D8S286,D8S164, CMT4A)-D8S84-tel. Families with types B and C were subsequently typed and linkage for these types was excluded for the CMT4A region and other known CMT loci. Recently, the gene for a major peripheral myelin protein (PMP2) was mapped by FISH to chromosome 8q21-q22 and therefore appeared to be a strong candidate gene for CMT4A. We used SSCP analysis, DNA sequencing, FISH and YAC mapping analysis, and demonstrated that PMP2 is not the defect in CMT4A. Using physical mapping data, we sublocalized a new genethon marker (D8S548) to the CMT4A region between D8S286 and D8S164. All affected CMT4A patients were homozygotes for this polymorphic microsatellite as expected from its physical localization. We screened the CEPH megabase YAC library using the closest markers; over 30 YACs were isolated and characterized by PFGE. FISH analysis revealed about 16% chimeras. The YACs span the 8 cM region between D8S279 and PMP2 (mapped distal to D8S84), with a current 1 cM gap between D8S164 and D8S84. We are currently using Alu-PCR and vectorette to develop end clones in order to identify new YACs in the region and further close this gap. Alu-PCR fragments have identified several new microsatellites in the region which can be used for additional mapping of the CMT4A gene.

  13. Charcot Marie Tooth disease (CMT): historical perspectives and evolution.

    PubMed

    Kazamel, Mohamed; Boes, Christopher J

    2015-01-01

    Prior to Charcot and Marie's and Tooth's reports, patients with peroneal muscular atrophy had been described by Virchow, Eulenburg, Friedreich, Osler, and others. In February 1886, Charcot and Marie published their original description of five patients who had what they called Progressive Muscular Atrophy. They surmised that the lesion could be in the spinal cord. Three months later, Tooth presented his M.D. degree thesis entitled "Peroneal Type of Progressive Muscular Atrophy", to the University of Cambridge, UK. Tooth localized the pathology to the peripheral nerves. Dyck and Lambert (Arch Neurol 18:619-625, 1968) classified several CMT kinships based on differences in modes of inheritance, natural history, biochemical features, nerve conduction velocity, and pathologic characteristics. This article will focus on historical landmarks and major discoveries pertinent to the disease since its original description through the second half of the twentieth century.

  14. A chemically modified tetracycline (CMT-3) is a new antifungal agent.

    PubMed

    Liu, Yu; Ryan, Maria E; Lee, Hsi-Ming; Simon, Sanford; Tortora, George; Lauzon, Carol; Leung, Michael K; Golub, Lorne M

    2002-05-01

    Several chemically modified tetracycline analogs (CMTs), which were chemically modified to eliminate their antibacterial efficacy, were unexpectedly found to have antifungal properties. Of 10 CMTs screened in vitro, all exhibited antifungal activities, although their efficacies varied. Among these compounds, CMT-315, -3, and -308 were found to be the most potent as antifungal agents. The MICs of CMT-3 against 47 strains of fungi in vitro were determined by using amphotericin B (AMB) and doxycycline as positive and negative controls, respectively. The MICs of CMT-3 were generally found to be between 0.25 and 8.00 microg/ml, a range that approximates the blood levels of this drug when administrated orally to humans. Of all the yeast species tested to date, Candida albicans showed the greatest sensitivity to CMT-3. The filamentous species most susceptible to CMT-3 were found to be Epidermophyton floccosum, Microsporum gypseum, Pseudallescheria boydii, a Penicillium sp., Scedosporium apiospermum, a Tricothecium sp., and Trichophyton rubrum. Growth inhibition of C. albicans by CMT-3, determined by a turbidity assay, indicated a 50% inhibitory concentration of 1 microg/ml. Thirty-nine strains, including 20 yeasts and 19 molds, were used to measure viability (the ability to grow after treatment with a drug) inhibition by CMT-3 and AMB. CMT-3 exhibited fungicidal activity against most of these fungi, especially the filamentous fungi. Eighty-four percent (16 of 19) of the filamentous fungi tested showed more than 90% inhibition of viability by CMT-3. In contrast, AMB showed fungicidal activity against all yeasts tested. However, most of the filamentous fungi (16 of 19) showed less than 50% inhibition of viability by AMB, indicating that AMB is fungistatic against most of these filamentous fungi. To begin to identify the sites in fungal cells affected by CMT-3, C. albicans and a Penicillium sp. were incubated with the compound at 35 degrees C, and then the fluorescence of

  15. Charcot-Marie-Tooth (CMT) disease 1A with superimposed inflammatory polyneuropathy in children.

    PubMed

    Desurkar, A; Lin, J-P; Mills, K; Al-Sarraj, S; Jan, W; Jungbluth, H; Wraige, E

    2009-04-01

    Charcot-Marie-Tooth (CMT) disease is genetically heterogeneous and subdivided into demyelinating (CMT 1) and axonal (CMT 2) types based on neurophysiology findings. CMT1A, the commonest form associated with duplication of the PMP22 segment on chromosome 17p, often arises in childhood but is generally a slowly progressive disease. We report 2 children presenting with clinical features of an acute inflammatory demyelinating polyneuropathy (AIDP) who were subsequently diagnosed with underlying CMT1A. Both children had neurophysiology and histopathology features consistent with CMT1. Immunoglobulin treatment was initiated considering the evidence of superimposed inflammation and appeared to modify disease progression. Our findings indicate that CMT1A predisposes to a superimposed inflammatory neuropathy. Recognition of this association is difficult, particularly in children without clear family history, but of great importance as immunomodulatory treatment may improve outcome. In addition, we postulate that an underlying genetic polyneuropathy should be suspected if the recovery from AIDP is slower than expected, or incomplete. (c) Georg Thieme Verlag KG Stuttgart, New York.

  16. Reliability and validity of the CMT neuropathy score as a measure of disability.

    PubMed

    Shy, M E; Blake, J; Krajewski, K; Fuerst, D R; Laura, M; Hahn, A F; Li, J; Lewis, R A; Reilly, M

    2005-04-12

    To determine the validity and reliability of the Charcot-Marie-Tooth disease (CMT) neuropathy score (CMTNS) in patients with inherited neuropathy. Natural history studies and potential treatment trials for patients with various forms of CMT are limited by the lack of quantitative methodologies to monitor disease progression. Most cases of CMT can be considered length-dependent axonal neuropathies because disability for even the demyelinating forms correlates with length-dependent axonal degeneration. The total neuropathy score (TNS) is a validated composite measure of disability in length-dependent axonal neuropathies but is weighted toward predominantly sensory neuropathies. Thus, the authors have devised a CMTNS, modified from the TNS, to provide a single measure to quantify CMT disability. The authors measured inter- and intrainvestigator reliability of the CMTNS and performed a validation of the score with the Neuropathy Impairment Score (NIS), patient self-assessment scores, an ambulation index, and other measures of disability. Inter- and intrainvestigator reliability was more than 95% in the 60 patients evaluated. Patients could be divided into mild (CMTNS, < or =10), moderate (CMTNS, 11 to 20), and severe (CMTNS, > or =21) categories and demonstrated excellent correlations among all measures of disability. The Charcot-Marie-Tooth disease (CMT) neuropathy score is a validated measure of length-dependent axonal and demyelinating CMT disability and can be investigated as an end point for longitudinal studies and clinical trials of CMT.

  17. Responsiveness of gait analysis parameters in a cohort of 71 CMT subjects.

    PubMed

    Lencioni, Tiziana; Piscosquito, Giuseppe; Rabuffetti, Marco; Bovi, Gabriele; Di Sipio, Enrica; Diverio, Manuela; Moroni, Isabella; Padua, Luca; Pagliano, Emanuela; Schenone, Angelo; Pareyson, Davide; Ferrarin, Maurizio

    2017-07-14

    Detection of worsening in the slowly progressive Charcot-Marie-Tooth disease (CMT) is difficult. As previous clinical scales showed low responsiveness, novel outcome measures are under study, including innovative approaches such as quantitative muscle MRI and instrumented movement analysis. Since gait analysis proved able to reliably quantify CMT locomotor deficits, we aimed to explore whether it can be a sensitive-to-change outcome measure in CMT studies. Clinical and biomechanical evaluations were performed in 71 CMT subjects at baseline and after a mean (±sd) of 28.9 ± 9.5 months. Locomotor tasks included natural walking, ascending and descending steps. Instrumented analysis of such tasks provided indexes related to muscle strength (kinetic parameters) and joint movement (kinematic parameters). Parameter responsiveness was expressed as Standardized Response Mean (SRM). Considering the whole CMT group, several parameters showed moderate responsiveness; subgrouping subjects according to disease severity allowed reaching high responsiveness (SRM >0.80). CMT Examination Score showed moderate responsiveness (SRM 0.53) in the minimally affected group; kinematic parameters were more responsive in this group, whereas kinetic parameters in the most severely affected one. Biomechanical parameters can represent suitable outcome measures for CMT by showing moderate-to-high responsiveness. These data suggest that appropriate selection of patient population and outcome measures is crucial for clinical trials' design. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. LINC complex alterations in DMD and EDMD/CMT fibroblasts.

    PubMed

    Taranum, Surayya; Vaylann, Eva; Meinke, Peter; Abraham, Sabu; Yang, Liu; Neumann, Sascha; Karakesisoglou, Iakowos; Wehnert, Manfred; Noegel, Angelika A

    2012-08-01

    Emery-Dreifuss muscular dystrophy (EDMD) is a late onset-disease characterized by skeletal muscle wasting and heart defects with associated risk of sudden death. The autosomal dominant form of the disease is caused by mutations in the LMNA gene encoding LaminA and C, the X-linked form results from mutations in the gene encoding the inner nuclear membrane protein Emerin (STA). Both Emerin and LaminA/C interact with the nuclear envelope proteins Nesprin-1 and -2 and mutations in genes encoding C-terminal isoforms of Nesprin-1 and -2 have also been implicated in EDMD. Here we analyse primary fibroblasts from patients affected by either Duchenne muscular dystrophy (DMD) or Emery-Dreifuss muscular dystrophy/Charcot-Marie-Tooth syndrome (EDMD/CMT) that in addition to the disease causing mutations harbour mutations in the Nesprin-1 gene and in the SUN1 and SUN2 gene, respectively. SUN proteins together with the Nesprins form the core of the LINC complex which connects the nucleus with the cytoskeleton. The mutations are accompanied by changes in cell adhesion, cell migration, senescence, and stress response, as well as in nuclear shape and nuclear envelope composition which are changes characteristic for laminopathies. Our results point to a potential influence of mutations in components of the LINC complex on the clinical outcome and the molecular pathology in the patients. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Transgenic mouse models of CMT1A and HNPP.

    PubMed

    Suter, U; Nave, K A

    1999-09-14

    We have generated several PMP22 animal mutants with altered PMP22 gene dosage. A moderate increase in the number of PMP22 genes led to hypomyelination comparable to CMT1A, whereas high copy numbers of transgenic PMP22 resulted in phenotypes resembling more severe forms of hereditary motor and sensory neuropathies. In contrast, eliminating one of the two normal PMP22 genes by gene targeting caused unstable focal hypermyelination (tomacula) similar to the pathology in HNPP. A related but more severe phenotype was observed in mice that lack PMP22 completely. Detailed analysis of the different PMP22 mutants revealed, in addition to the obvious myelinopathy, distal axonopathy as a characteristic feature. We conclude that the maintenance of axons might be a promising target for therapeutic interventions in these demyelinating hereditary neuropathies. Furthermore, our results strongly support the concept that PMP22-related neuropathies (and most likely also other forms of inherited motor and sensory neuropathies) should be viewed as the consequence of impaired neuron-Schwann cell interactions that are likely already to be operative during development. Such considerations should be taken into account in the design of potential novel treatment strategies.

  20. Molecular mechanisms for CMT1A duplication and HNPP deletion.

    PubMed

    Boerkoel, C F; Inoue, K; Reiter, L T; Warner, L E; Lupski, J R

    1999-09-14

    As the best characterized human genomic disorders, CMT1A and HNPP illustrate several common mechanistic features of genomic rearrangements. These features include the following: (1) Recombination occurs between homologous sequences flanking the duplicated/deleted genomic segment. (2) The evolution of the mammalian genome may result in an architecture consisting of region-specific low-copy repeats that predispose to rearrangement secondary to providing homologous regions as substrate for recombination. (3) Strand exchange occurs preferentially in a region of perfect sequence identity within the flanking repeat sequences. (4) Double-strand breaks likely initiate recombination between the flanking repeats. (5) The mechanism and rate of homologous recombination resulting in DNA rearrangement may differ for male and female gametogenesis. (6) Homologous recombination resulting in DNA rearrangement occurs with high frequency in the human genome. (7) Genomic disorders result from structural features of the human genome and not population specific alleles or founder effects; therefore, genomic disorders appear to occur with equal frequencies in different world populations.

  1. Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease.

    PubMed

    Murphy, Sinéad M; Herrmann, David N; McDermott, Michael P; Scherer, Steven S; Shy, Michael E; Reilly, Mary M; Pareyson, Davide

    2011-09-01

    The Charcot-Marie-Tooth neuropathy score (CMTNS) is a reliable and valid composite score comprising symptoms, signs, and neurophysiological tests, which has been used in natural history studies of CMT1A and CMT1X and as an outcome measure in treatment trials of CMT1A. Following an international workshop on outcome measures in Charcot-Marie-Tooth disease (CMT), the CMTNS was modified to attempt to reduce floor and ceiling effects and to standardize patient assessment, aiming to improve its sensitivity for detecting change over time and the effect of an intervention. After agreeing on the modifications made to the CMTNS (CMTNS2), three examiners evaluated 16 patients to determine inter-rater reliability; one examiner evaluated 18 patients twice within 8 weeks to determine intra-rater reliability. Three examiners evaluated 63 patients using the CMTNS and the CMTNS2 to determine how the modifications altered scoring. For inter- and intra-rater reliability, intra-class correlation coefficients (ICCs) were ≥0.96 for the CMT symptom score and the CMT examination score. There were small but significant differences in some of the individual components of the CMTNS compared with the CMTNS2, mainly in the components that had been modified the most. A longitudinal study is in progress to determine whether the CMTNS2 is more sensitive than the CMTNS for detecting change over time.

  2. Chemically modified tetracycline-3 (CMT-3): a novel inhibitor of the serine proteinase, elastase.

    PubMed

    Gu, Ying; Lee, Hsi-Ming; Simon, Sanford R; Golub, Lorne M

    2011-12-01

    Two classes of enzymes play an important role in connective tissue breakdown during various inflammatory diseases: serine proteinases and matrix metalloproteinases (MMPs). Tetracyclines (TCs) exhibit important anti-inflammatory and MMP-inhibitory properties that are unrelated to their antibacterial activities. Of the various TCs and their chemically modified NON-antibiotic analogs (CMTs) tested in vitro and in vivo, CMT-3 (6-demethyl-6-deoxy 4 de-dimethylamino tetracycline) has repeatedly been shown to be the most potent inhibitor of MMP activity and cytokine production. In addition to its anti-MMP function, we have shown that among all CMTs, CMT-3 is the only CMT that can also directly inhibit both the amidolytic activity of human leukocyte elastase (HLE, a serine proteinase) and the extracellular matrix degradation mediated by HLE. In addition, CMT-3 has been found to reduce leukocyte elastase activity in vivo in gingival extracts of rats with experimental periodontal disease. Thus, CMT-3 can inhibit pathologic connective tissue breakdown by (at least) two mechanisms: direct inhibition of neutral proteinases (elastase and MMPs); and protecting their endogenous inhibitors, α(1)-PI and TIMPs, from being digested and inactivated by MMPs and HLE, respectively. The pleiotropic properties of CMT-3 including (but not limited to) inhibition of serine proteinases, MMPs, and cytokines provide impressive therapeutic potential to reduce excessive connective tissue breakdown during various pathologic processes including inflammatory diseases, cancer metastasis and metabolic bone diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Rapid diagnosis of CMT1A duplications and HNPP deletions by multiplex microsatellite PCR.

    PubMed

    Choi, Byung-Ok; Kim, Joonki; Lee, Kyung Lyong; Yu, Jin Seok; Hwang, Jung Hee; Chung, Ki Wha

    2007-02-28

    Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are frequent forms of genetically heterogeneous peripheral neuropathies. Reciprocal unequal crossover between flanking CMT1A-REPs on chromosome 17p11.2-p12 is a major cause of CMT type 1A (CMT1A) and HNPP. The importance of a sensitive and rapid method for identifying the CMT1A duplication and HNPP deletion is being emphasized. In the present study, we established a molecular diagnostic method for the CMT1A duplication and HNPP deletion based on hexaplex PCR of 6 microsatellite markers (D17S921, D17S9B, D17S9A, D17S918, D17S4A and D17S2230). The method is highly time-, cost- and sample-saving because the six markers are amplified by a single PCR reaction and resolved with a single capillary in 3 h. Several statistical and forensic estimates indicated that most of these markers are likely to be useful for diagnosing the peripheral neuropathies. Reproducibility, as determined by concordance between independent tests, was estimated to be 100%. The likelihood that genotypes of all six markers are homozygous in randomly selected individuals was calculated to be 1.6 x 10(-4) which indicates that the statistical error rate for this diagnosis of HNPP deletion is only 0.016%.

  4. Validation of the CMT Pediatric Scale as an outcome measure of disability

    PubMed Central

    Burns, Joshua; Ouvrier, Robert; Estilow, Tim; Shy, Rosemary; Laurá, Matilde; Pallant, Julie F.; Lek, Monkol; Muntoni, Francesco; Reilly, Mary M.; Pareyson, Davide; Acsadi, Gyula; Shy, Michael E.; Finkel, Richard S.

    2012-01-01

    Objective Charcot-Marie-Tooth disease (CMT) is a common heritable peripheral neuropathy. There is no treatment for any form of CMT although clinical trials are increasingly occurring. Patients usually develop symptoms during the first two decades of life but there are no established outcome measures of disease severity or response to treatment. We identified a set of items that represent a range of impairment levels and conducted a series of validation studies to build a patient-centered multi-item rating scale of disability for children with CMT. Methods As part of the Inherited Neuropathies Consortium, patients aged 3–20 years with a variety of CMT types were recruited from the USA, UK, Italy and Australia. Initial development stages involved: definition of the construct, item pool generation, peer review and pilot testing. Based on data from 172 patients, a series of validation studies were conducted, including: item and factor analysis, reliability testing, Rasch modeling and sensitivity analysis. Results Seven areas for measurement were identified (strength, dexterity, sensation, gait, balance, power, endurance), and a psychometrically robust 11-item scale constructed (Charcot-Marie-Tooth disease Pediatric Scale: CMTPedS). Rasch analysis supported the viability of the CMTPedS as a unidimensional measure of disability in children with CMT. It showed good overall model fit, no evidence of misfitting items, no person misfit and it was well targeted for children with CMT. Interpretation The CMTPedS is a well-tolerated outcome measure that can be completed in 25-minutes. It is a reliable, valid and sensitive global measure of disability for children with CMT from the age of 3 years. PMID:22522479

  5. Ascorbic acid in Charcot–Marie–Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial

    PubMed Central

    Pareyson, Davide; Reilly, Mary M; Schenone, Angelo; Fabrizi, Gian Maria; Cavallaro, Tiziana; Santoro, Lucio; Vita, Giuseppe; Quattrone, Aldo; Padua, Luca; Gemignani, Franco; Visioli, Francesco; Laurà, Matilde; Radice, Davide; Calabrese, Daniela; Hughes, Richard AC; Solari, Alessandra

    2011-01-01

    Summary Background Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 (PMP22), a model of Charcot–Marie–Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Methods Adult patients (aged 18–70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). Findings We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the

  6. Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial.

    PubMed

    Pareyson, Davide; Reilly, Mary M; Schenone, Angelo; Fabrizi, Gian Maria; Cavallaro, Tiziana; Santoro, Lucio; Vita, Giuseppe; Quattrone, Aldo; Padua, Luca; Gemignani, Franco; Visioli, Francesco; Laurà, Matilde; Radice, Davide; Calabrese, Daniela; Hughes, Richard A C; Solari, Alessandra

    2011-04-01

    Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 (PMP22), a model of Charcot-Marie-Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Adult patients (aged 18-70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the ascorbic acid group and 13·9 (4·2) in

  7. Chemically modified tetracycline (CMT)-3 inhibits histamine release and cytokine production in mast cells: possible involvement of protein kinase C.

    PubMed

    Sandler, C; Ekokoski, E; Lindstedt, K A; Vainio, P J; Finel, M; Sorsa, T; Kovanen, P T; Golub, L M; Eklund, K K

    2005-07-01

    To find novel inhibitors of mast cell function we have studied the effect of a potent, non-antimicrobial, chemically modified tetracycline, CMT-3 or COL-3, on key functions of mast cells. In the presence of 25 microM CMT-3, the 48/80-induced histamine release from rat serosal mast cells was inhibited significantly, to 43.0 +/- 7.3% of control. Similarly, the activation-induced secretion of TNF-alpha and IL-8 by HMC-1 cells were decreased in the presence of 25 microM CMT-3 to 13.5 +/- 4.1% and 9.7 +/- 1.1% of control, respectively. CMT-3 did not cause intracellular accumulation of TNF-alpha but instead it reduced the expression of TNF-alpha mRNA in HMC-1 cells. Moreover, CMT-3 was found to significantly inhibit the protein kinase C (PKC) activity with IC(50) value of 31 microM. CMT-3 inhibited effectively both human recombinant PKCalpha and PKCdelta isoforms. In comparison to doxycycline, CMT-3 was more effective as an inhibitor of both cytokine production and PKC activity. Considering the central role of PKC in mast cell activation, PKC inhibition could, at least partially, explain the observed inhibitory effects of CMT-3. The inhibition of the key proinflammatory functions of mast cells by CMT-3 suggests its potential clinical usefulness in the treatment of allergic and inflammatory disorders.

  8. Unilateral oculomotor palsy in Charcot-Marie-Tooth disease 1A (CMT 1A).

    PubMed

    Posa, A; Emmer, A; Kornhuber, M E

    2017-04-01

    Charcot-Marie-Tooth disease (CMT) type 1A is the most common form of CMT 1 and one of the autosomal dominant demyelinating hereditary motor and sensory neuropathies (HMSN). Cranial nerves may be frequently subclinically affected in CMT disease. However manifest clinical signs of cranial nerve involvement are rare. This case comprise neurological, ophthalmological, internal medicine and ear-nose-throat investigation, motor and sensory nerve conduction velocity, auditory evoked potentials and orbicularis-oculi reflex measurements, lumbar puncture and blood examination, inclusive molecular genetic testing, as well as electrocardiogram and cranial imaging such as computer tomography and magnetic resonance imaging RESULTS: The present case shows a Charcot-Marie-Tooth (CMT) 1A patient with complete unilateral oculomotor palsy in combination with predominant ipsilateral subclinical trigeminal demyelination. A combined of third and fifth cranial nerves as in our patient has not been reported yet. This case shows cranial nerve involvement as an unusual leading symptom of CMT 1A. It may remind us that hereditary neuropathies have to be taken into consideration in patients with slowly progressing unilateral or asymmetric cranial neuropathies. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Variables influencing quality of life and disability in Charcot Marie Tooth (CMT) patients: Italian multicentre study.

    PubMed

    Padua, L; Aprile, I; Cavallaro, T; Commodari, I; La Torre, G; Pareyson, D; Quattrone, A; Rizzuto, N; Vita, G; Tonali, P; Schenone, A

    2006-12-01

    The purpose of this study was to assess the variables that influence quality of life (QoL) and disability in patients with Charcot-Marie-Tooth disease (CMT). We performed a prospective multicentre study using validated clinical disability and QoL measurements. Multivariate analysis was performed using QoL as a dependent variable and duration of symptoms, age, gender and CMT type, depression and disability measurements as independent variables. We enrolled 211 patients. QoL was highly significantly deteriorated with respect to the Italian normative sample. The physical aspect of QoL was mainly related to disability but it does not increase with the age, probably because of an adaptation between expectation and reality. The mental QoL is influenced by depression (hence we have to consider this aspect approaching CMT patients). Moreover, we observed that women complained of more severe symptoms than men. Finally, some CMT subtypes are related to more severe bodily pain symptoms than others. Multiperspective assessment of CMT showed new aspects of this disease, mainly regarding (1) differences between men and women and (2) the crucial role of pain and depression.

  10. Al-Si-Mn Alloy Coating on Aluminum Substrate Using Cold Metal Transfer (CMT) Welding Technique

    NASA Astrophysics Data System (ADS)

    Rajeev, G. P.; Kamaraj, M.; Bakshi, S. R.

    2014-06-01

    The cold metal transfer (CMT) process was explored as a weld overlay technique for synthesizing Al-Si-Mn alloy coating on a commercially pure Al plate. The effect of welding speed on the bead geometry, deposition rate, and the dilution were studied and the best parameter was used to synthesize the coatings. The CMT process can be used to produce thick coatings (>2.5 mm) without porosity and with low dilution levels. The Vickers hardness number of the Al substrate increased from 28 in the bulk to 57 in the coating. It is suggested that the CMT process can be an effective and energy-efficient technique for depositing thick coatings and is useful in weld repair of aluminum alloy components.

  11. Factors Affecting Phenotype Variability in a Family with CMT2B: Gender and LRSAM1 Genotype

    PubMed Central

    Peddareddygari, Leema Reddy; Oberoi, Kinsi; Vellore, Jaasrini Reddy; Grewal, Raji P.

    2016-01-01

    Charcot-Marie-Tooth disease type 2 (CMT2) is an autosomal dominant axonal neuropathy caused by mutations in various genes. The subtype CMT2B results from missense mutations in RAB7A, member RAS oncogene family gene, whereas missense mutations in the Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) gene cause CMT2P. We describe the genotype/phenotype analysis of a family in which a previously described mutation in the RAB7A gene and a novel mutation in the LRSAM1 gene were identified. In this family, none of the individuals had ulceromutilating features, and there was a marked variability in the age of onset. We discuss the possible etiology of the observed phenotypic variability including the role of gender and possible RAB7A/LRSAM1 gene interactions. PMID:27462242

  12. Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E.

    PubMed

    Pisciotta, Chiara; Bai, Yunhong; Brennan, Kathryn M; Wu, Xingyao; Grider, Tiffany; Feely, Shawna; Wang, Suola; Moore, Steven; Siskind, Carly; Gonzalez, Michael; Zuchner, Stephan; Shy, Michael E

    2015-07-21

    To investigate the effects of NEFL Glu396Lys mutation on the expression and assembly of neurofilaments (NFs) in cutaneous nerve fibers of patients with Charcot-Marie-Tooth disease type 2E (CMT2E). A large family with CMT2E underwent clinical, electrophysiologic, and skin biopsy studies. Biopsies were processed by indirect immunofluorescence (IF), electron microscopy (EM), and Western blot analysis. The clinical features demonstrated intrafamilial phenotypic variability, and the electrophysiologic findings revealed nerve conductions that were either slow or in the intermediate range. All patients had reduced or absent compound muscular action potential amplitudes. Skin biopsies showed axons labeled with the axonal markers protein gene product 9.5 and α-tubulin, but not with NFs. The results of Western blot analysis were consistent with those of IF, showing reduced or absent NFs and normal expression of α-tubulin. EM revealed clusters of regenerated fibers, in absence of myelin sheath abnormalities. Both IF and EM failed to show NF aggregates in dermal axons. The morphometric analysis showed a smaller axonal caliber in patients than in controls. The study of the nodal/paranodal architecture demonstrated that sodium channels and Caspr were correctly localized in patients with CMT2E. Decrease in NF abundance may be a pathologic marker of CMT2E. The lack of NF aggregates, consistent with prior studies, suggests that they occur proximally leading to subsequent alterations in the axonal cytoskeleton. The small axonal caliber, along with the normal molecular architecture of nodes and paranodes, explain the reduced velocities detected in patients with CMT2E. Our results also demonstrate that skin biopsy can provide evidence of pathologic and pathogenic abnormalities in patients with CMT2E. © 2015 American Academy of Neurology.

  13. Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E

    PubMed Central

    Bai, Yunhong; Brennan, Kathryn M.; Wu, Xingyao; Grider, Tiffany; Feely, Shawna; Wang, Suola; Moore, Steven; Siskind, Carly; Gonzalez, Michael; Zuchner, Stephan; Shy, Michael E.

    2015-01-01

    Objective: To investigate the effects of NEFL Glu396Lys mutation on the expression and assembly of neurofilaments (NFs) in cutaneous nerve fibers of patients with Charcot-Marie-Tooth disease type 2E (CMT2E). Methods: A large family with CMT2E underwent clinical, electrophysiologic, and skin biopsy studies. Biopsies were processed by indirect immunofluorescence (IF), electron microscopy (EM), and Western blot analysis. Results: The clinical features demonstrated intrafamilial phenotypic variability, and the electrophysiologic findings revealed nerve conductions that were either slow or in the intermediate range. All patients had reduced or absent compound muscular action potential amplitudes. Skin biopsies showed axons labeled with the axonal markers protein gene product 9.5 and α-tubulin, but not with NFs. The results of Western blot analysis were consistent with those of IF, showing reduced or absent NFs and normal expression of α-tubulin. EM revealed clusters of regenerated fibers, in absence of myelin sheath abnormalities. Both IF and EM failed to show NF aggregates in dermal axons. The morphometric analysis showed a smaller axonal caliber in patients than in controls. The study of the nodal/paranodal architecture demonstrated that sodium channels and Caspr were correctly localized in patients with CMT2E. Conclusions: Decrease in NF abundance may be a pathologic marker of CMT2E. The lack of NF aggregates, consistent with prior studies, suggests that they occur proximally leading to subsequent alterations in the axonal cytoskeleton. The small axonal caliber, along with the normal molecular architecture of nodes and paranodes, explain the reduced velocities detected in patients with CMT2E. Our results also demonstrate that skin biopsy can provide evidence of pathologic and pathogenic abnormalities in patients with CMT2E. PMID:26109717

  14. Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies.

    PubMed

    Østern, Rune; Fagerheim, Toril; Hjellnes, Helene; Nygård, Bjørn; Mellgren, Svein I; Nilssen, Øivind

    2013-09-21

    Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. However, in a diagnostic laboratory setting relying on external test requisitions and patient samples, such conditions are not always met. Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quality and applicability with regard to the recommended algorithms for CMT diagnostics. As we are the main test centre for CMT in Norway our results also provide an overview of the spectrum of gene defects in the Norwegian CMT population. Genetic testing was performed according to polyneuropathy type; demyelinating/mixed: PMP22 duplication, MPZ, EGR2, LITAF, NEFL, PMP22, GJB1, axonal: MFN2, MPZ, NEFL, and GJB1. Diagnostic testing of index patients was requested in 435 of the 549 cases. Seventy-two (16.6%) positive molecular genetic findings were made. The majority (94.6%) of mutation positive cases showed disease onset before 50 years of age. PMP22 (duplication), MPZ, GJB1 and MFN2 mutations constituted 95.8% of the positive findings. Within the nerve conduction study groups, mutation detection rates were; demyelinating 33.8%; mixed 29.0%; axonal 8.8%; unspecified 16.5%. We suggest a simplified algorithm intended for referral centres, dealing with DNA/blood samples, which involves the assessment of age at onset and neurophysiological data followed by testing of four genes; PMP22 (duplication), MPZ, GJB1 and MFN2. Patients negative for mutations in those four genes should be subjected to evaluation at an interdisciplinary inherited neuropathy clinic with the capacity for extended molecular genetic analysis by next generation sequencing.

  15. Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies

    PubMed Central

    2013-01-01

    Background Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. However, in a diagnostic laboratory setting relying on external test requisitions and patient samples, such conditions are not always met. Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quality and applicability with regard to the recommended algorithms for CMT diagnostics. As we are the main test centre for CMT in Norway our results also provide an overview of the spectrum of gene defects in the Norwegian CMT population. Methods Genetic testing was performed according to polyneuropathy type; demyelinating/mixed: PMP22 duplication, MPZ, EGR2, LITAF, NEFL, PMP22, GJB1, axonal: MFN2, MPZ, NEFL, and GJB1. Results Diagnostic testing of index patients was requested in 435 of the 549 cases. Seventy-two (16.6%) positive molecular genetic findings were made. The majority (94.6%) of mutation positive cases showed disease onset before 50 years of age. PMP22 (duplication), MPZ, GJB1 and MFN2 mutations constituted 95.8% of the positive findings. Within the nerve conduction study groups, mutation detection rates were; demyelinating 33.8%; mixed 29.0%; axonal 8.8%; unspecified 16.5%. Conclusion We suggest a simplified algorithm intended for referral centres, dealing with DNA/blood samples, which involves the assessment of age at onset and neurophysiological data followed by testing of four genes; PMP22 (duplication), MPZ, GJB1 and MFN2. Patients negative for mutations in those four genes should be subjected to evaluation at an interdisciplinary inherited neuropathy clinic with the capacity for extended molecular genetic analysis by next generation sequencing. PMID:24053775

  16. MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families.

    PubMed

    Braathen, Geir J; Sand, Jette C; Lobato, Ana; Høyer, Helle; Russell, Michael B

    2010-03-29

    Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included. We screened for point mutations in the MFN2 gene. We identified four known and three novel point mutations in 8 unrelated CMT families. The novel point mutations were not found in 100 healthy controls. This corresponds to 3.4% (8/232) of CMT families have point mutations in the MFN2 gene. The phenotypes were compatible with CMT1 in two families, CMT2 in four families, intermediate CMT in one family and distal Hereditary Motor Neuropathy (dHMN) in one family. This corresponds to 2.3% of CMT1, 5.5% of CMT2, 12.5% of intermediate CMT and 6.7% of dHMN families have a point mutation in the MFN2 gene. Point mutations in the MFN2 gene is likely to be the fourth most common cause to CMT after duplication of the peripheral myelin protein 22 (PMP22) gene, and point mutations in the Connexin32 (Cx32) and myelin protein zero (MPZ) genes. The identified known and novel point mutations in the MFN2 gene expand the clinical spectrum from CMT2 and intermediate CMT to also include possibly CMT1 and the dHMN phenotypes. Thus, genetic analyses of the MFN2 gene should not be restricted to persons with CMT2.

  17. MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families

    PubMed Central

    2010-01-01

    Background Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. Methods Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included. We screened for point mutations in the MFN2 gene. Results We identified four known and three novel point mutations in 8 unrelated CMT families. The novel point mutations were not found in 100 healthy controls. This corresponds to 3.4% (8/232) of CMT families have point mutations in the MFN2 gene. The phenotypes were compatible with CMT1 in two families, CMT2 in four families, intermediate CMT in one family and distal Hereditary Motor Neuropathy (dHMN) in one family. This corresponds to 2.3% of CMT1, 5.5% of CMT2, 12.5% of intermediate CMT and 6.7% of dHMN families have a point mutation in the MFN2 gene. Point mutations in the MFN2 gene is likely to be the fourth most common cause to CMT after duplication of the peripheral myelin protein 22 (PMP22) gene, and point mutations in the Connexin32 (Cx32) and myelin protein zero (MPZ) genes. Conclusions The identified known and novel point mutations in the MFN2 gene expand the clinical spectrum from CMT2 and intermediate CMT to also include possibly CMT1 and the dHMN phenotypes. Thus, genetic analyses of the MFN2 gene should not be restricted to persons with CMT2. PMID:20350294

  18. Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease.

    PubMed

    Huang, Jia; Wu, Xingyao; Montenegro, Gladys; Price, Justin; Wang, Gaofeng; Vance, Jeffery M; Shy, Michael E; Züchner, Stephan

    2010-05-01

    Hereditary peripheral neuropathies present a group of clinically and genetically heterogeneous entities. All known forms, including the various forms of Charcot-Marie-Tooth disease (CMT) are characterized as Mendelian traits and over 35 genes have been identified thus far. The mutational mechanism of the most common CMT type, CMT1A, is a 1.5 Mb chromosomal duplication at 17p12 that contains the gene PMP22. Only recently it has been realized that such copy number variants (CNV) are a widespread phenomenon and important for disease. However, it is not known whether CNVs play a wider role in hereditary peripheral neuropathies outside of CMT1A. In a phenotypically heterogeneous sample of 97 patients, we performed the first high-density CNV study of 34 genomic regions harboring known genes for hereditary peripheral neuropathies including the 17p12 duplication region, with comparative genomic hybridization (CGH) microarrays. We identified three CNVs that affected coding exons. A novel shorter form of a PMP22 duplication was detected in a CMT1A family previously tested negative in a commercial test. Two other CNVs in MTMR2 and ARHGEF10 are likely not disease associated. Our results indicate that CNVs are a rare cause for non-CMT1A CMT. Their potential relevance as disease modifiers remains to be evaluated. The present study design cannot rule out that specific CMT forms exist where CNVs play a larger role.

  19. Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2.

    PubMed

    Houlden, H; Laura, M; Wavrant-De Vrièze, F; Blake, J; Wood, N; Reilly, M M

    2008-11-18

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder and is characterized by significant clinical and genetic heterogeneity. Recently, mutations in both the small heat shock protein 27 (HSP27 or HSPB1) and 22 (HSP22 or HSPB8) genes have been reported to cause autosomal dominant CMT with minimal sensory involvement (CMT 2F/CMT2L) and autosomal dominant distal hereditary motor neuropathy type II (dHMN II). We analyzed the HSPB1 and HSPB8 genes in a large clinically well-characterized series of dHMN and CMT type 2 (CMT2) cases and families using linkage analysis and direct sequencing of these genes. We identified a novel homozygous mutation in the alpha-crystallin domain of HSPB1 segregating in an autosomal recessive fashion in a family with distal HMN/CMT2. A further four heterozygous HSPB1 mutations were identified in four autosomal dominant families dHMN/CMT2, and two sporadic cases were identified with probable de novo mutations. In the autosomal dominant and autosomal recessive families, there were no clinical sensory findings, but reduced sural nerve action potential amplitudes were found in some affected individuals, indicating that long sensory axons are mildly affected in this predominantly motor disorder. This extends the clinical and electrophysiologic spectrum of HSPB1 mutations and identifies four unreported dominant HSPB1 mutations and the first family where the HSPB1 mutation acts in a recessive way to cause distal HMN.

  20. Topically applied CMT-2 enhances wound healing in streptozotocin diabetic rat skin.

    PubMed

    Ramamurthy, N S; Kucine, A J; McClain, S A; McNamara, T F; Golub, L M

    1998-11-01

    Delayed wound healing is one of the complications of diabetes mellitus, exhibited by increased wound collagenase and decreased granulation tissues. The current study compared wound healing in normal and diabetic rats, and the effects of topically applied 1% or 3% concentrations of chemically modified tetracycline-2 (CMT-2) on 6-mm circular full-thickness skin wounds healed by secondary intention. On day 7 after wounding, tissues were removed for biochemical analysis and histology. The wound granulation tissue hydroxyproline was less in the untreated diabetic rat with increased collagenase and gelatinase. Treating the diabetic rat wounds with 3% CMT-2 increased the wound hydroxyproline and decreased activities of gelatinase and collagenase. There was a delay in wound filling by granulation tissue in diabetic rats. In CMT-2-treated diabetic rats, the volume of granulation tissue was greater than that in untreated diabetic rats. CMT-2 appears to normalize wound healing in diabetic rats and may be a valuable adjunct in the treatment of chronic wounds.

  1. Metagenome and metatranscriptome data for Rifle CMT-03 laboratory microcosm experiment completed in April 2014

    DOE Data Explorer

    Jewell, Talia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Karaoz, Ulas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Bill, Markus [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chakraborty, Romy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Brodie, Eoin L [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Williams, Kenneth Hurst [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Beller, Harry R [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-04-01

    Sediment samples were collected during installation of monitoring borehole CMT-03. Microcosms were constructed and inoculated under anerobic conditions with these sediments and anaerobic Rifle artificial groundwater. Microcosm metagenomes and metatranscriptomes were sampled every 5 days for a period of 20 days. The dataset gives gene-level annotations, binning, metagenomic and metatranscriptomic coverages for these microcosms.

  2. Empowering Cooperating Teachers: The University of Alabama Clinical Master Teacher (CMT) Program.

    ERIC Educational Resources Information Center

    Stanford, Ronnie L.; And Others

    In the Clinical Master Teacher (CMT) program of the University of Alabama's College of Education, CMTs are outstanding elementary, middle, and secondary school teachers elected to participate in an innovative teacher intern (student teacher) supervisory program. They are empowered to fulfill the traditional roles of both the campus-based college…

  3. Computer Mediated Communications Inside a Classroom: A Study Using CMT Technology with ELT Students.

    ERIC Educational Resources Information Center

    Vance, Kathleen Center; Fitzpatrick, Dale; Sackville, Patricia

    1997-01-01

    Describes the use of CMT (computer-mediated communications) to help ELT (English-language training, or English-as-a-Second-Language (ESL) students at the British Columbia Institute of Technology (BCIT) acquire high-level communication, cultural, and employability skills as well as language skills for postsecondary studies and employment. (LRW)

  4. Detection of mosaicism in a CMT1a patient using FISH

    SciTech Connect

    Sourour, E.; Thompson, P.; MacMillan, J.; Upadhyaya, M.

    1994-09-01

    Charcot-Marie-Tooth disease type 1 (CMT1) is the most common hereditary motor and sensory neuropathy, and is characterized by peroneal muscular atrophy, pes cavus, loss of deep tendon reflexes and reduced motor nerve conduction velocities. CMT1a segregates as an autosomal dominant condition and shows complete linkage and association with a large submicroscopic duplication on chromosome 17p11.2-p12. We have detected a mosaicism in the father of an affected CMT1a patient. The affected individuals in this family were found to be homozygous with DNA markers YAW409, p132GBRI which are duplicated in CMT1a patients. FISH analysis with YAC clone (Y49H7), carried on 45 interphases from the affected father, revealed that the duplication was only present in 24 of these interphases. However, this duplication was found in all 50 interphases screened from the father`s affected son and, as expected, none of the 50 interphases derived from a non-CMT case had any evidence of this duplication. The affected father had had difficulty with his balance from age 40, with numerous falls. His median and motor nerve conduction velocities were normal. There was no obvious history fo the disorder in the previous generations. The affected boy had foot drop prior to his 10th birthday. He had loss of sensation in his feet and sensorineural deafness from childhood and had a median motor conduction velocity of 33 meters/second. The findings based on FISH analysis suggest that the mosaicism may have occurred early in embryogenesis leading to the disease in the father.

  5. Dimerization is required for GARS-mediated neurotoxicity in dominant CMT disease.

    PubMed

    Malissovas, Nikos; Griffin, Laurie B; Antonellis, Anthony; Beis, Dimitris

    2016-04-15

    Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of peripheral neuropathies. Mutations in several aminoacyl-tRNA synthetase (ARS) genes have been implicated in inherited CMT disease. There are 12 reported CMT-causing mutations dispersed throughout the primary sequence of the human glycyl-tRNA synthetase (GARS). While there is strong genetic evidence linking GARS mutations to CMT disease, the molecular pathology underlying the neuromuscular and sensory phenotypes is still not fully understood. In particular, it is unclear whether the mutations result in a toxic gain of function, a partial loss of activity related to translation, or a combination of these mechanisms. We identified a zebrafish allele of gars (gars(s266)). Homozygous mutant embryos carry a C->A transversion, that changes a threonine to a lysine, in a residue next to a CMT-associated human mutation. We show that the neuromuscular phenotype observed in animals homozygous for T209K Gars (T130K in GARS) is due to a loss of dimerization of the mutated protein. Furthermore, we show that the loss of function, dimer-deficient and human disease-associated G319R Gars (G240R in GARS) mutant protein is unable to rescue the above phenotype. Finally, we demonstrate that another human disease-associated mutant G605R Gars (G526 in GARS) dimerizes with the remaining wild-type protein in animals heterozygous for the T209K Gars and reduces the function enough to elicit a neuromuscular phenotype. Our data indicate that dimerization is required for the dominant neurotoxicity of disease-associated GARS mutations and provide a rapid, tractable model for studying newly identified GARS variants for a role in human disease. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H

    PubMed Central

    Houlden, Henry; Hammans, Simon; Katifi, Haider; Reilly, Mary M.

    2009-01-01

    Background: Charcot Marie Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies. CMT4H is an early onset autosomal recessive demyelinating neuropathy. The locus responsible for CMT4H was assigned to chromosome 12p11.21-q13.11 by homozygosity mapping and mutations in the Frabin gene (FGD4 Rho GDP/GTP exchange factor) were subsequently identified in six families. Methods: We sequenced the Frabin gene in a cohort of 12 UK CMT families with clinically defined autosomal recessive demyelinating neuropathy. Results: We identified a novel homozygous Frabin p.R275X mutation in a family from Northern Ireland. The two affected cases in this family had a very slowly progressive neuropathy with both cases remaining ambulant into middle age. Examination of mRNA from lymphoblasts showed that this stop mutation caused very little nonsense mediated mRNA decay and the predominant mRNA species was the mutant form that is likely to be translated into a truncated protein. Conclusions: This work extends the understanding of the pathogenesis of Frabin mutation-associated Charcot Marie Tooth (CMT) 4H and suggests that mutations in Frabin should also be considered in ambulant adults with CMT1. GLOSSARY AR = autosomal recessive; CMT = Charcot Marie Tooth; MCV = motor conduction velocity; MRC = Medical Research Council; NMD = nonsense mediated mRNA decay. PMID:19221294

  7. High frequency of mutations in codon 98 of the peripheral myelin protein Po gene in 20 French CMT1 patients

    SciTech Connect

    Rougher, H.; LeGuern, E. Gouider, R.

    1996-03-01

    Charcot-Marie-Tooth disease, characterized by distal muscle weakness and amyotrophy, decreased or absent tendon reflexes, and high arched feet, is the most common inherited peripheral neuropathy, with a prevalence of 1 in 2,500. Two types of CMT have been distinguished on the basis of nerve conduction velocities. CMT type 1 is the most frequent, with markedly slowed velocities ({<=}40 m/s) associated with hypertrophic onion bulb changes on nerve biopsy. Autosomal dominant CMT1 is genetically heterogeneous: CMT1A is caused by a 1.5-Mb duplication in 17p11.2 and, more rarely, by a point mutation in tha PMP22 (peripheral myelin protein, 22 kD) gene located in the duplicated region; CMT1B results from mutations in the Po (peripheral myelin protein zero) gene in 1q22-23. Forty-five percent (7/16) of the published mutations associated with CMT1 occur in exon 3 of Po. In order to determine the cause of CMT1 in 20 unrelated patients without 17p11.2 duplications, mutations were sought in exon 3 of Po with three techniques: nonradioactive SSCP, automated sequencing, and PCR enzymatic restriction. 18 refs., 2 figs.

  8. Biochemical characterization of protein quality control mechanisms during disease progression in the C22 mouse model of CMT1A

    PubMed Central

    Chittoor, Vinita G.; Sooyeon, Lee; Rangaraju, Sunitha; Nicks, Jessica R.; Schmidt, Jordan T.; Madorsky, Irina; Narvaez, Diana C.; Notterpek, Lucia

    2013-01-01

    Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary demyelinating neuropathy linked with duplication of the peripheral myelin protein 22 (PMP22) gene. Transgenic C22 mice, a model of CMT1A, display many features of the human disease, including slowed nerve conduction velocity and demyelination of peripheral nerves. How overproduction of PMP22 leads to compromised myelin and axonal pathology is not fully understood, but likely involves subcellular alterations in protein homoeostatic mechanisms within affected Schwann cells. The subcellular response to abnormally localized PMP22 includes the recruitment of the ubiquitin–proteasome system (UPS), autophagosomes and heat-shock proteins (HSPs). Here we assessed biochemical markers of these protein homoeostatic pathways in nerves from PMP22-overexpressing neuropathic mice between the ages of 2 and 12 months to ascertain their potential contribution to disease progression. In nerves of 3-week-old mice, using endoglycosidases and Western blotting, we found altered processing of the exogenous human PMP22, an abnormality that becomes more prevalent with age. Along with the ongoing accrual of misfolded PMP22, the activity of the proteasome becomes compromised and proteins required for autophagy induction and lysosome biogenesis are up-regulated. Moreover, cytosolic chaperones are consistently elevated in nerves from neuropathic mice, with the most prominent change in HSP70. The gradual alterations in protein homoeostatic response are accompanied by Schwann cell de-differentiation and macrophage infiltration. Together, these results show that while subcellular protein quality control mechanisms respond appropriately to the presence of the overproduced PMP22, with aging they are unable to prevent the accrual of misfolded proteins. PMID:24175617

  9. Demyelinating CMT--what's known, what's new and what's in store?

    PubMed

    Brennan, Kathryn M; Bai, Yunhong; Shy, Michael E

    2015-06-02

    Inherited neuropathies known collectively as Charcot-Marie-Tooth disease are one of the most common inherited neurological conditions affecting ∼1 in 2500 people. A heterogenous disorder, CMT is divided into subtypes based on the pattern of inheritance and also by neurophysiological studies. Despite the clinical similarities among patients with demyelinating CMT, it is recognized that this group of disorders is both genetically and phenotypically heterogenous. Understanding the pathogenesis of these disorders requires an intimate knowledge of normal myelin development and homeostasis. Improvements in genetic testing techniques over the last 20 years have contributed majorly to the identification of specific genes, proteins, and molecular pathways that are providing the basis for understanding the disease processes and developing rational approaches to therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis

    PubMed Central

    Fridman, V; Bundy, B; Reilly, M M; Pareyson, D; Bacon, C; Burns, J; Day, J; Feely, S; Finkel, R S; Grider, T; Kirk, C A; Herrmann, D N; Laurá, M; Li, J; Lloyd, T; Sumner, C J; Muntoni, F; Piscosquito, G; Ramchandren, S; Shy, R; Siskind, C E; Yum, S W; Moroni, I; Pagliano, E; Zuchner, S; Scherer, S S; Shy, M E

    2015-01-01

    Background The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. Methods We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). Results 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. Conclusions Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. Clinical trial registration ID number NCT01193075. PMID:25430934

  11. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.

    PubMed

    Fridman, V; Bundy, B; Reilly, M M; Pareyson, D; Bacon, C; Burns, J; Day, J; Feely, S; Finkel, R S; Grider, T; Kirk, C A; Herrmann, D N; Laurá, M; Li, J; Lloyd, T; Sumner, C J; Muntoni, F; Piscosquito, G; Ramchandren, S; Shy, R; Siskind, C E; Yum, S W; Moroni, I; Pagliano, E; Zuchner, S; Scherer, S S; Shy, M E

    2015-08-01

    The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. ID number NCT01193075. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Expressing hNF-LE397K results in abnormal gaiting in a transgenic model of CMT2E

    PubMed Central

    Dale, Jeffrey M.; Villalon, Eric; Shannon, Stephen G.; Barry, Devin M.; Markey, Rachel M.; Garcia, Virginia B.; Garcia, Michael L.

    2012-01-01

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gaiting, exacerbation of neuropathy, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing a hNF-LE397K transgene, which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we demonstrated that hNF-LE397K mice developed abnormal gait of the hind limbs. The identification of severe gaiting defects in combination with previously observed muscle atrophy, reduced axon caliber, and decreased nerve conduction velocity suggests that hNF-LE397K mice recapitulate many of clinical signs associated with CMT2E. Therefore, hNF-LE397K mice provide a context for potential therapeutic intervention. PMID:22288874

  13. A 71-nucleotide deletion in the periaxin gene in a Romani patient with early-onset slowly progressive demyelinating CMT.

    PubMed

    Baránková, L; Sisková, D; Hühne, K; Vyhnálková, E; Sakmaryová, I; Bojar, M; Rautenstrauss, B; Seeman, P

    2008-06-01

    Mutations in the periaxin (PRX) gene cause autosomal recessive demyelinating neuropathy Charcot-Marie-Tooth (CMT) type 4F. To date, 10 non-sense or frameshift PRX mutations have been reported in patients with early-onset neuropathy and further disease course consistent with either Dejerine-Sottas neuropathy or slow-progressive demyelinating CMT. We sequenced 59 patients from 55 Czech families including four unrelated patients of Romani (Gypsy) origin with early-onset CMT displaying decreased nerve conduction velocities. We identified a novel homozygous mutation c.3286_3356del71 (K1095fsX18) in one Romani patient showing very slow disease progression. Amongst non-Romani Czech CMT patients, PRX mutations have been proven to be very rare.

  14. Mutation analysis of the nerve specific promoter of the peripheral myelin protein 22 gene in CMT1 disease and HNPP.

    PubMed

    Nelis, E; De Jonghe, P; De Vriendt, E; Patel, P I; Martin, J J; Van Broeckhoven, C

    1998-07-01

    We analysed the nerve specific promoter of the peripheral myelin protein 22 gene (PMP22) in a set of 15 unrelated patients with Charcot-Marie-Tooth type 1 disease (CMT1) and 16 unrelated patients with hereditary neuropathy with liability to pressure palsies (HNPP). In these patients no duplication/deletion nor a mutation in the coding region of the CMT1/ HNPP genes was detected. In one autosomal dominant CMT1 patient, we identified a base change in the non-coding exon 1A of PMP22 which, however, did not cosegregate with the disease in the family. This study indicates that mutations in the nerve specific PMP22 promoter and 5' untranslated exon will not be a common genetic cause of CMT1A and HNPP.

  15. Mutations in the LMNA gene do not cause axonal CMT in Czech patients.

    PubMed

    Lassuthová, Petra; Baránková, Lucia; Haberlová, Jana; Mazanec, Radim; Wallace, Andrew; Huehne, Kathrin; Rautenstrauss, Bernd; Seeman, Pavel

    2009-06-01

    The LMNA gene was sequenced in 98 Czech patients from 94 unrelated families with early-onset axonal Charcot-Marie-Tooth (CMT) disease consistent with both autosomal recessive inheritance and sporadic cases. Biallelic pathogenic mutations were not found in any patient in this group. One patient carried the c.1870C>T mutation that is predicted to result in the amino-acid substitution, p. Arg624Cys, on one allele, but the second causative mutation was not detected. LMNA mutation is not likely to be associated with the disease in this family. To exclude larger deletions/duplications in the LMNA gene not detectable by sequencing, 48 patients from this group were also analyzed with multiplex ligation-dependent probe amplification. No rearrangements in the LMNA gene were detected. We conclude that mutations in the LMNA gene are absent from a large group of Czech patients with axonal autosomal recessive CMT disease. Consequently, LMNA mutation screening does not seem to be relevant for axonal CMT DNA diagnostics. A similar situation may apply to other European populations.

  16. CMT: a constrained multi-level thresholding approach for ChIP-Seq data analysis.

    PubMed

    Rezaeian, Iman; Rueda, Luis

    2014-01-01

    Genome-wide profiling of DNA-binding proteins using ChIP-Seq has emerged as an alternative to ChIP-chip methods. ChIP-Seq technology offers many advantages over ChIP-chip arrays, including but not limited to less noise, higher resolution, and more coverage. Several algorithms have been developed to take advantage of these abilities and find enriched regions by analyzing ChIP-Seq data. However, the complexity of analyzing various patterns of ChIP-Seq signals still needs the development of new algorithms. Most current algorithms use various heuristics to detect regions accurately. However, despite how many formulations are available, it is still difficult to accurately determine individual peaks corresponding to each binding event. We developed Constrained Multi-level Thresholding (CMT), an algorithm used to detect enriched regions on ChIP-Seq data. CMT employs a constraint-based module that can target regions within a specific range. We show that CMT has higher accuracy in detecting enriched regions (peaks) by objectively assessing its performance relative to other previously proposed peak finders. This is shown by testing three algorithms on the well-known FoxA1 Data set, four transcription factors (with a total of six antibodies) for Drosophila melanogaster and the H3K4ac antibody dataset.

  17. Niacin-mediated Tace activation ameliorates CMT neuropathies with focal hypermyelination.

    PubMed

    Bolino, Alessandra; Piguet, Françoise; Alberizzi, Valeria; Pellegatta, Marta; Rivellini, Cristina; Guerrero-Valero, Marta; Noseda, Roberta; Brombin, Chiara; Nonis, Alessandro; D'Adamo, Patrizia; Taveggia, Carla; Previtali, Stefano Carlo

    2016-12-01

    Charcot-Marie-Tooth (CMT) neuropathies are highly heterogeneous disorders caused by mutations in more than 70 genes, with no available treatment. Thus, it is difficult to envisage a single suitable treatment for all pathogenetic mechanisms. Axonal Neuregulin 1 (Nrg1) type III drives Schwann cell myelination and determines myelin thickness by ErbB2/B3-PI3K-Akt signaling pathway activation. Nrg1 type III is inhibited by the α-secretase Tace, which negatively regulates PNS myelination. We hypothesized that modulation of Nrg1 levels and/or secretase activity may constitute a unifying treatment strategy for CMT neuropathies with focal hypermyelination as it could restore normal levels of myelination. Here we show that in vivo delivery of Niaspan, a FDA-approved drug known to enhance TACE activity, efficiently rescues myelination in the Mtmr2(-/-) mouse, a model of CMT4B1 with myelin outfoldings, and in the Pmp22(+/-) mouse, which reproduces HNPP (hereditary neuropathy with liability to pressure palsies) with tomacula. Importantly, we also found that Niaspan reduces hypermyelination of Vim (vimentin)(-/-) mice, characterized by increased Nrg1 type III and Akt activation, thus corroborating the hypothesis that Niaspan treatment downregulates Nrg1 type III signaling. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  18. CMT: A Constrained Multi-Level Thresholding Approach for ChIP-Seq Data Analysis

    PubMed Central

    Rezaeian, Iman; Rueda, Luis

    2014-01-01

    Genome-wide profiling of DNA-binding proteins using ChIP-Seq has emerged as an alternative to ChIP-chip methods. ChIP-Seq technology offers many advantages over ChIP-chip arrays, including but not limited to less noise, higher resolution, and more coverage. Several algorithms have been developed to take advantage of these abilities and find enriched regions by analyzing ChIP-Seq data. However, the complexity of analyzing various patterns of ChIP-Seq signals still needs the development of new algorithms. Most current algorithms use various heuristics to detect regions accurately. However, despite how many formulations are available, it is still difficult to accurately determine individual peaks corresponding to each binding event. We developed Constrained Multi-level Thresholding (CMT), an algorithm used to detect enriched regions on ChIP-Seq data. CMT employs a constraint-based module that can target regions within a specific range. We show that CMT has higher accuracy in detecting enriched regions (peaks) by objectively assessing its performance relative to other previously proposed peak finders. This is shown by testing three algorithms on the well-known FoxA1 Data set, four transcription factors (with a total of six antibodies) for Drosophila melanogaster and the H3K4ac antibody dataset. PMID:24736605

  19. Characterization of methane hydrate host sediments using synchrotron-computed microtomography (CMT)

    USGS Publications Warehouse

    Jones, K.W.; Feng, H.; Tomov, S.; Winters, W.J.; Prodanovic, M.; Mahajan, D.

    2007-01-01

    The hydrate-sediment interaction is an important aspect of gas hydrate studies that needs further examination. We describe here the applicability of the computed microtomography (CMT) technique that utilizes an intense X-ray synchrotron source to characterize sediment samples, two at various depths from the Blake Ridge area (a well-known hydrate-prone region) and one from Georges Bank, that once contained methane trapped as hydrates. Detailed results of the tomographic analysis performed on the deepest sample (667??m) from Blake Ridge are presented as 2-D and 3-D images which show several mineral constituents, the internal grain/pore microstructure, and, following segmentation into pore and grain space, a visualization of the connecting pathways through the pore-space of the sediment. Various parameters obtained from the analysis of the CMT data are presented for all three sediment samples. The micro-scale porosity values showed decreasing trend with increasing depth for all three samples that is consistent with the previously reported bulk porosity data. The 3-D morphology, pore-space pathways, porosity, and permeability values are also reported for all three samples. The application of CMT is now being expanded to the laboratory-formed samples of hydrate in sediments as well as field samples of methane hydrate bearing sediments.

  20. Ultrasonic shear wave velocity in CLF/CMT graphite from room temperature to 2000/sup 0/F

    SciTech Connect

    Gieske, J.H.

    1980-11-01

    The temperature dependence of the ultrasonic shear velocity in CLF/CMT graphite was determined from room temperature to 2000/sup 0/F using a pulse-echo technique. Data are presented for five 0.75-inch-diameter specimens all machined from the same CLF/CMT billet. Plots of ultrasonic pulse-echo radial and axial scans of the billet which characterize the material property uniformity of the billet are also given.

  1. A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H.

    PubMed

    Houlden, Henry; Hammans, Simon; Katifi, Haider; Reilly, Mary M

    2009-02-17

    Charcot Marie Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies. CMT4H is an early onset autosomal recessive demyelinating neuropathy. The locus responsible for CMT4H was assigned to chromosome 12p11.21-q13.11 by homozygosity mapping and mutations in the Frabin gene (FGD4 Rho GDP/GTP exchange factor) were subsequently identified in six families. We sequenced the Frabin gene in a cohort of 12 UK CMT families with clinically defined autosomal recessive demyelinating neuropathy. We identified a novel homozygous Frabin p.R275X mutation in a family from Northern Ireland. The two affected cases in this family had a very slowly progressive neuropathy with both cases remaining ambulant into middle age. Examination of mRNA from lymphoblasts showed that this stop mutation caused very little nonsense mediated mRNA decay and the predominant mRNA species was the mutant form that is likely to be translated into a truncated protein. This work extends the understanding of the pathogenesis of Frabin mutation-associated Charcot Marie Tooth (CMT) 4H and suggests that mutations in Frabin should also be considered in ambulant adults with CMT1.

  2. Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy.

    PubMed

    Chumakov, Ilya; Milet, Aude; Cholet, Nathalie; Primas, Gwenaël; Boucard, Aurélie; Pereira, Yannick; Graudens, Esther; Mandel, Jonas; Laffaire, Julien; Foucquier, Julie; Glibert, Fabrice; Bertrand, Viviane; Nave, Klaus-Armin; Sereda, Michael W; Vial, Emmanuel; Guedj, Mickaël; Hajj, Rodolphe; Nabirotchkin, Serguei; Cohen, Daniel

    2014-12-10

    Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited sensory and motor peripheral neuropathy. It is caused by PMP22 overexpression which leads to defects of peripheral myelination, loss of long axons, and progressive impairment then disability. There is no treatment available despite observations that monotherapeutic interventions slow progression in rodent models. We thus hypothesized that a polytherapeutic approach using several drugs, previously approved for other diseases, could be beneficial by simultaneously targeting PMP22 and pathways important for myelination and axonal integrity. A combination of drugs for CMT1A polytherapy was chosen from a group of authorised drugs for unrelated diseases using a systems biology approach, followed by pharmacological safety considerations. Testing and proof of synergism of these drugs were performed in a co-culture model of DRG neurons and Schwann cells derived from a Pmp22 transgenic rat model of CMT1A. Their ability to lower Pmp22 mRNA in Schwann cells relative to house-keeping genes or to a second myelin transcript (Mpz) was assessed in a clonal cell line expressing these genes. Finally in vivo efficacy of the combination was tested in two models: CMT1A transgenic rats, and mice that recover from a nerve crush injury, a model to assess neuroprotection and regeneration. Combination of (RS)-baclofen, naltrexone hydrochloride and D-sorbitol, termed PXT3003, improved myelination in the Pmp22 transgenic co-culture cellular model, and moderately down-regulated Pmp22 mRNA expression in Schwannoma cells. In both in vitro systems, the combination of drugs was revealed to possess synergistic effects, which provided the rationale for in vivo clinical testing of rodent models. In Pmp22 transgenic CMT1A rats, PXT3003 down-regulated the Pmp22 to Mpz mRNA ratio, improved myelination of small fibres, increased nerve conduction and ameliorated the clinical phenotype. PXT3003 also improved axonal regeneration and

  3. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: Implications for testing in the cytogenetics laboratory

    SciTech Connect

    Shaffer, L.G.; Kennedy, G.M.; Spikes, A.S.

    1997-03-31

    Charcot-Marie-Tooth (CMT) disease type 1A is an inherited peripheral neuropathy characterized by slowly progressive distal muscle wasting and weakness, decreased nerve conduction velocities, and genetic linkage to 17p12. Most (>98%) CMT1A cases are caused by a DNA duplication of a 1.5-Mb region in 17p12 containing the PMP22 gene. The reciprocal product of the CMT1A duplication is a 1.5-Mb deletion which causes hereditary neuropathy with liability to pressure palsies (HNPP). The most informative current diagnostic testing requires pulsed-field gel electrophoresis to detect DNA rearrangement-specific junction fragments. We investigated the use of interphase FISH for the detection of duplications and deletions for these disorders in the clinical molecular cytogenetics laboratory. Established cell lines or blood specimens from 23 individuals with known molecular diagnoses and 10 controls were obtained and scored using a two-color FISH assay. At least 70%, of CMT1A cells displayed three signals consistent with duplications. Using this minimum expected percentile to make a CMT1A duplication diagnosis, all patients with CMT1A showed a range of 71-92% of cells displaying at least three signals. Of the HNPP cases, 88% of cells displayed only one hybridization signal, consistent with deletions. The PMP22 locus from normal control individuals displayed a duplication pattern in {approximately}9% of cells, interpreted as replication of this locus. The percentage of cells showing replication was significantly lower than in those cells displaying true duplications. We conclude that FISH can be reliably used to diagnose CMT1A and HNPP in the clinical cytogenetics laboratory and to readily distinguish the DNA rearrangements associated with these disorders from individuals without duplication or deletion of the PMP22 locus. 43 refs., 4 figs., 2 tabs.

  4. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: implications for testing in the cytogenetics laboratory.

    PubMed

    Shaffer, L G; Kennedy, G M; Spikes, A S; Lupski, J R

    1997-03-31

    Charcot-Marie-Tooth (CMT) disease type 1A is an inherited peripheral neuropathy characterized by slowly progressive distal muscle wasting and weakness, decreased nerve conduction velocities, and genetic linkage to 17p12. Most (> 98%) CMT1A cases are caused by a DNA duplication of a 1.5-Mb region in 17p12 containing the PMP22 gene. The reciprocal product of the CMT1A duplication is a 1.5-Mb deletion which causes hereditary neuropathy with liability to pressure palsies (HNPP). The most informative current diagnostic testing requires pulsed-field gel electrophoresis to detect DNA rearrangement-specific junction fragments. We investigated the use of interphase FISH for the detection of duplications and deletions for these disorders in the clinical molecular cytogenetics laboratory. Established cell lines or blood specimens from 23 individuals with known molecular diagnoses and 10 controls were obtained and scored using a two-color FISH assay. At least 70% of CMT1A cells displayed three signals consistent with duplications. Using this minimum expected percentile to make a CMT1A duplication diagnosis, all patients with CMT1A showed a range of 71-92% of cells displaying at least three signals. Of the HNPP cases, 88% of cells displayed only one hybridization signal, consistent with deletions. The PMP22 locus from normal control individuals displayed a duplication pattern in approximately 9% of cells, interpreted as replication of this locus. The percentage of cells showing replication was significantly lower than in those cells displaying true duplications. We conclude that FISH can be reliably used to diagnose CMT1A and HNPP in the clinical cytogenetics laboratory and to readily distinguish the DNA rearrangements associated with these disorders from individuals without duplication or deletion of the PMP22 locus.

  5. A case of CMT 1B due to Val 102/fs null mutation of the MPZ gene presenting as hyperCKemia.

    PubMed

    Luigetti, M; Modoni, A; Renna, R; Silvestri, G; Ricci, E; Montano, N; Tasca, G; Papacci, M; Monforte, M; Conte, A; Pomponi, M G; Sabatelli, M

    2010-11-01

    Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A, due to a duplication in the gene encoding the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P0) account for demyelinating CMT1B. Herein, we report a patient presenting with an isolated hyperCKemia in whom electrophysiological and pathological findings revealed a demyelinating and axonal neuropathy. Sequencing of the MPZ gene revealed a 306delA at codon 102 in the proband and in two relatives. This mutation has been already described in association with paucisymptomatic CMT without hyperCKemia. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Effects of 3D Earth structure on W-phase CMT parameters

    NASA Astrophysics Data System (ADS)

    Morales, Catalina; Duputel, Zacharie; Rivera, Luis; Kanamori, Hiroo

    2017-04-01

    The source inversion of the W-phase has demonstrated a great potential to provide fast and reliable estimates of the centroid moment tensor (CMT) for moderate to large earthquakes. It has since been implemented in different operational environments (NEIC-USGS, PTWC, etc.) with the aim of providing rapid CMT solutions. These solutions are in particular useful for tsunami warning purposes. Computationally, W-phase waveforms are usually synthetized by summation of normal modes at long period (100 - 1000 s) for a spherical Earth model (e.g., PREM). Although the energy of these modes mainly stays in the mantle where lateral structural variations are relatively small, the impact of 3D heterogeneities on W-phase solutions have not yet been quantified. In this study, we investigate possible bias in W-phase source parameters due to unmodeled lateral structural heterogeneities. We generate a simulated dataset consisting of synthetic seismograms of large past earthquakes that accounts for the Earth's 3D structure. The W-phase algorithm is then used to invert the synthetic dataset for earthquake CMT parameters with and without added noise. Results show that the impact of 3D heterogeneities is generally larger for surface-waves than for W-phase waveforms. However, some discrepancies are noted between inverted W-phase parameters and target values. Particular attention is paid to the possible bias induced by the unmodeled 3D structure into the location of the W-phase centroid. Preliminary results indicate that the parameter that is most susceptible to 3D Earth structure seems to be the centroid depth.

  7. High Resolution X-ray CMT Imaging of Supercritical CO2 in Porous Media: Experimental Challenges, Solutions, and Results

    NASA Astrophysics Data System (ADS)

    Herring, A. L.; Andersson, L.; Newell, D. L.; Carey, J. W.; Wildenschild, D.

    2013-12-01

    Geologic carbon dioxide (CO2) sequestration has been proposed as a climate change mitigation strategy to limit emissions of CO2 to the atmosphere from large fossil-fuel burning CO2 point sources; however, there are concerns associated with the long-term stability of a mobile subsurface CO2 plume. Capillary trapping of supercritical CO2 (scCO2), wherein the CO2 is held within the pore structure of the geologic matrix by capillary forces, is a more secure form of subsurface storage than structural trapping, which relies on an impermeable caprock to contain the buoyant CO2 plume. To understand the multiphase physics of CO2 transport, and to subsequently produce quantitative estimates of potential CO2 capillary trapping, it is necessary to study field, core, and pore-scale processes. X-ray computed microtomography (x-ray CMT) allows for three-dimensional (3D) in-situ visualization of fluid phases within and the physical structure of a porous medium at the pore-scale. We have designed and built a mobile experimental set-up capable of running at pressures up to 2000 PSI and temperatures up to 50°C, made with materials that are compatible with corrosive fluids. Our experimental procedure includes pressurizing, mixing, and separating fluids; and subsequently running immiscible drainage and imbibition flow experiments with brine and supercritical CO2. With this set-up and procedure, we successfully conducted a brine-scCO2 drainage experiment in Bentheimer sandstone at 1200 PSI and 36°C, and confirmed and quantified CO2 flow in the sandstone core via synchrotron-based x-ray CMT with a resolution of 4.65 μm at the Advanced Photon Source at Argonne National Laboratory. We have proven that we can observe, on a pore-scale basis, the movement of supercritical CO2 within a porous media. The properties of supercritical CO2 (e.g. viscosity, density, interfacial tension and solubility in brine) vary significantly with changes in pressure and temperature; consequently, precise

  8. Intensive strength and balance training with the Kinect console (Xbox 360) in a patient with CMT1A.

    PubMed

    Pagliano, Emanuela; Foscan, Maria; Marchi, Alessia; Corlatti, Alice; Aprile, Giorgia; Riva, Daria

    2017-08-01

    Effective drugs for type 1A Charcot-Marie-Tooth (CMT1A) disease are not available. Various forms of moderate exercise are beneficial, but few data are available on the effectiveness of exercise in CMT1A children. To investigate the feasibility and effectiveness of exercises to improve ankle strength and limb function in a child with CMT1A. Outpatient clinic. Nine-year-old boy with CMT1A. The rehabilitation program consisted of ankle exercises and Kinect videogame-directed physical activities (using an Xbox 360 console/movement sensor) that aimed to improve balance and limb strength. The program was given 3 times a week for 5 weeks. The child was assessed at baseline, after 5 weeks, and 3 and 6 months after. By the end of follow-up, child balance and endurance had improved, but ankle strength did not. The encouraging results for balance and endurance justify further studies on videogame-directed activities in CMT1A children/adolescents.

  9. Tetracyclines and chemically modified tetracycline-3 (CMT-3) modulate cytokine secretion by lipopolysaccharide-stimulated whole blood.

    PubMed

    Cazalis, Julia; Tanabe, Shin-ichi; Gagnon, Guy; Sorsa, Timo; Grenier, Daniel

    2009-04-01

    In addition to their bacteriostatic effect, tetracyclines, which are often used in the treatment of periodontitis, also present anti-inflammatory properties. In the present study, we investigated the effects of tetracycline (TC), doxycycline (doxy), and chemically modified tetracycline-3 (CMT-3) on the production of pro-inflammatory mediators and matrix metalloproteinases (MMPs) in an ex vivo human whole blood (WB) model stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). WB samples obtained from three periodontitis patients and six healthy subjects were stimulated with P. gingivalis LPS in the absence and presence of TC, doxy, or CMT-3. The secretion of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), MMP-8, and MMP-9 by the WB samples was determined using enzyme-linked immunosorbent assays. P. gingivalis LPS significantly increased the secretion of all cytokines and MMPs tested. While we observed inter-patient variations, TC, doxy, and CMT-3 caused reductions of LPS-induced cytokine secretion to various degrees. TC, doxy, and CMT-3 had no significant effect on MMP-8 and MMP-9 secretion by LPS-stimulated WB samples. In conclusion, we used a human WB model that takes into consideration relevant in vivo immune cell interactions in the presence of plasma proteins to show that TC, doxy, and CMT-3 can reduce the production of pro-inflammatory mediators. This property may contribute to the clinically proven benefits of these molecules in the treatment of periodontitis and other chronic inflammatory diseases.

  10. Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A).

    PubMed

    Sereda, Michael W; Meyer zu Hörste, Gerd; Suter, Ueli; Uzma, Naureen; Nave, Klaus-Armin

    2003-12-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The predominant subtype, CMT-1A, accounts for more than 50% of all cases and is associated with an interstitial chromosomal duplication of 17p12 (refs. 2,3). We have generated a model of CMT-1A by introducing extra copies of the responsible disease gene, Pmp22 (encoding the peripheral myelin protein of 22 kDa), into transgenic rats. Here, we used this model to test whether progesterone, a regulator of the myelin genes Pmp22 and myelin protein zero (Mpz) in cultured Schwann cells, can modulate the progressive neuropathy caused by moderate overexpression of Pmp22. Male transgenic rats (n = 84) were randomly assigned into three treatment groups: progesterone, progesterone antagonist (onapristone) and placebo control. Daily administration of progesterone elevated the steady-state levels of Pmp22 and Mpz mRNA in the sciatic nerve, resulting in enhanced Schwann cell pathology and a more progressive clinical neuropathy. In contrast, administration of the selective progesterone receptor antagonist reduced overexpression of Pmp22 and improved the CMT phenotype, without obvious side effects, in wild-type or transgenic rats. Taken together, these data provide proof of principle that the progesterone receptor of myelin-forming Schwann cells is a promising pharmacological target for therapy of CMT-1A.

  11. Visual appearance and CMT score of foremilk of individual quarters in relation to cell count of cows milked automatically.

    PubMed

    Rasmussen, Morten D; Bjerring, Martin; Skjøth, Flemming

    2005-02-01

    The objectives of the study were: to evaluate the interaction between visual appearance and California mastitis test (CMT) score of the foremilk in relation to the cell count of the milk; to evaluate the consequences of sorting milk according to these criteria; and to explore whether visual appearance and CMT score of foremilk depended on the time interval between milkings. Measuring somatic cell count (SCC) in composite milk only and discarding milk above certain thresholds will not ensure that milk from all cows with visually abnormal foremilk is withheld from delivery. Low thresholds of SCC will reduce the frequency of cows with abnormal milk but increase the discarding of milk from cows with visually normal foremilk. CMT score of foremilk differentiated better between cows with high and low SCC in composite milk than visual inspection of foremilk. CMT scores of foremilk decreased with increasing interval between milkings within cow, whereas the visual appearance was independent of the interval. We propose that visual appearance of the foremilk should be kept as a criterion for sorting milk at time of milking. For test purposes, the use of visual appearance of foremilk for differentiation between normal and abnormal milk has to be done on multiple milkings. Additionally, CMT scoring of foremilk improves correct classification of normal and abnormal quarters and especially when including data from the previous milking.

  12. Loss of Coupling Distinguishes GJB1 Mutations Associated with CNS Manifestations of CMT1X from Those Without CNS Manifestations.

    PubMed

    Abrams, Charles K; Goman, Mikhail; Wong, Sarah; Scherer, Steven S; Kleopa, Kleopas A; Peinado, Alejandro; Freidin, Mona M

    2017-01-10

    CMT1X, an X-linked inherited neuropathy, is caused by mutations in GJB1, which codes for Cx32, a gap junction protein expressed by Schwann cells and oligodendrocytes. Many GJB1 mutations cause central nervous system (CNS) abnormality in males, including stable subclinical signs and, less often, short-duration episodes characterized by motor difficulties and altered consciousness. However, some mutations have no apparent CNS effects. What distinguishes mutations with and without CNS manifestations has been unclear. Here we studied a total of 14 Cx32 mutations, 10 of which are associated with florid episodic CNS clinical syndromes in addition to peripheral neuropathy. The other 4 mutations exhibit neuropathy without clinical or subclinical CNS abnormalities. These "PNS-only" mutations (Y151C, V181M, R183C and L239I) form gap junction plaques and produce levels of junctional coupling similar to those for wild-type Cx32. In contrast, mutants with CNS manifestations (F51L, E102del, V139M, R142Q, R142W, R164W T55I, R164Q and C168Y) either form no morphological gap junction plaques or, if they do, produce little or no detectable junctional coupling. Thus, PNS and CNS abnormalities may involve different aspects of connexin function.

  13. Loss of Coupling Distinguishes GJB1 Mutations Associated with CNS Manifestations of CMT1X from Those Without CNS Manifestations

    PubMed Central

    Abrams, Charles K.; Goman, Mikhail; Wong, Sarah; Scherer, Steven S.; Kleopa, Kleopas A.; Peinado, Alejandro; Freidin, Mona M.

    2017-01-01

    CMT1X, an X-linked inherited neuropathy, is caused by mutations in GJB1, which codes for Cx32, a gap junction protein expressed by Schwann cells and oligodendrocytes. Many GJB1 mutations cause central nervous system (CNS) abnormality in males, including stable subclinical signs and, less often, short-duration episodes characterized by motor difficulties and altered consciousness. However, some mutations have no apparent CNS effects. What distinguishes mutations with and without CNS manifestations has been unclear. Here we studied a total of 14 Cx32 mutations, 10 of which are associated with florid episodic CNS clinical syndromes in addition to peripheral neuropathy. The other 4 mutations exhibit neuropathy without clinical or subclinical CNS abnormalities. These “PNS-only” mutations (Y151C, V181M, R183C and L239I) form gap junction plaques and produce levels of junctional coupling similar to those for wild-type Cx32. In contrast, mutants with CNS manifestations (F51L, E102del, V139M, R142Q, R142W, R164W T55I, R164Q and C168Y) either form no morphological gap junction plaques or, if they do, produce little or no detectable junctional coupling. Thus, PNS and CNS abnormalities may involve different aspects of connexin function. PMID:28071741

  14. Natural CMT2 Variation Is Associated With Genome-Wide Methylation Changes and Temperature Seasonality

    PubMed Central

    Shen, Xia; De Jonge, Jennifer; Forsberg, Simon K. G.; Pettersson, Mats E.; Sheng, Zheya; Hennig, Lars; Carlborg, Örjan

    2014-01-01

    As Arabidopsis thaliana has colonized a wide range of habitats across the world it is an attractive model for studying the genetic mechanisms underlying environmental adaptation. Here, we used public data from two collections of A. thaliana accessions to associate genetic variability at individual loci with differences in climates at the sampling sites. We use a novel method to screen the genome for plastic alleles that tolerate a broader climate range than the major allele. This approach reduces confounding with population structure and increases power compared to standard genome-wide association methods. Sixteen novel loci were found, including an association between Chromomethylase 2 (CMT2) and temperature seasonality where the genome-wide CHH methylation was different for the group of accessions carrying the plastic allele. Cmt2 mutants were shown to be more tolerant to heat-stress, suggesting genetic regulation of epigenetic modifications as a likely mechanism underlying natural adaptation to variable temperatures, potentially through differential allelic plasticity to temperature-stress. PMID:25503602

  15. GDAP1 mutations in Czech families with early-onset CMT.

    PubMed

    Baránková, L; Vyhnálková, E; Züchner, S; Mazanec, R; Sakmaryová, I; Vondrácek, P; Merlini, L; Bojar, M; Nelis, E; De Jonghe, P; Seeman, P

    2007-06-01

    Mutations in the ganglioside-induced differentiation associated protein-1 gene (GDAP1) cause autosomal recessive (AR) demyelinating or axonal Charcot-Marie-Tooth neuropathy (CMT). In order to establish the spectrum and frequency of GDAP1 mutations in Czech population, we sequenced GDAP1 in 74 Czech patients from 69 unrelated families with early-onset demyelinating or axonal CMT compatible with AR inheritance. We identified three isolated patients with GDAP1 mutations in both alleles. In one additional sporadic and one familial case, the second pathogenic mutation remained unknown. Overall, we detected two different mutations, a novel R191X nonsense and a L239F missense mutation. L239F previously described in a German-Italian family is a prevalent mutation in Czech population and we give evidence for its common ancestral origin. All Czech GDAP1 patients developed involvement of all four limbs evident by the end of second decade, except for one isolated patient showing very slow disease progression. All patients displayed axonal type of neuropathy.

  16. MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease.

    PubMed

    Lee, Y C; Yu, C T R; Lin, K P; Chang, M H; Hsu, S L; Liu, Y F; Lu, Y C; Soong, B W

    2008-01-22

    To characterize the clinical and cellular phenotypes of a novel MPZ mutation identified in a Chinese family with Charcot-Marie-Tooth (CMT) disease type 1B. The family was evaluated clinically, electrophysiologically, pathologically, and genetically. The wild-type and mutant P(0) fused with fluorescent proteins were expressed in vitro to monitor their intracellular trafficking. Adhesion assay was also performed to evaluate the adhesiveness of cells. The novel MPZ mutation, c.367G>A, is associated with a late-onset demyelinating CMT phenotype with autosomal dominant inheritance. The median motor nerve conduction velocities of patients in this family ranged from 15.7 to 19.6 m/second. The neuropathologic studies from a sural nerve biopsy revealed a severe loss of myelinated fibers, and some onion bulb formation with clusters of regenerative fibers. Fluorescence analysis demonstrated that the mutant protein was retained ectopically in the endoplasmic reticulum and Golgi apparatus. Adhesion assay demonstrated a defective adhesiveness of cells expressing the mutant P(0)G123S protein. The novel P(0)G123S mutation is associated with typical findings of late-onset demyelinating polyneuropathy in the electrophysiologic and pathologic studies, putatively resulting from aberrant intracellular trafficking of the mutant P(0) protein, which compromises the adhesiveness of the cells.

  17. Relationship between clinical examination, quality of life, disability and depression in CMT patients: Italian multicenter study.

    PubMed

    Padua, L; Aprile, I; Cavallaro, T; Commodari, I; Pareyson, D; Quattrone, A; Rizzuto, N; Vita, G; Tonali, P; Schenone, A

    2008-06-01

    To assess which are the clinical examination tests that are more related to quality of life (QoL), depression, and disability in CMT patients. Large prospective multicenter study through the use of validated clinical, disability, and QoL measurements. Correlations between clinical pattern and disability/QoL and depression were studied. Departments of Neurology. 211 CMT patients (60% females, mean age 42.5 years). None. Sensory function was related to both mental and physical aspects of patient's QoL. Ability to walk on toes and heels was related to physical aspects of QoL/disability but also to bodily pain. Strength of forearm/hand intrinsic muscles was related to disability and physical aspects of QoL. Some clinical tests may be better outcome measures than others because they are related to aspects of life highly relevant to the patients. This information may be useful in clinical practice and in clinical trials to infer the patient's QoL.

  18. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

    SciTech Connect

    Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M. ); Middleton, L.T. )

    1993-08-01

    Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.

  19. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase

    PubMed Central

    He, Weiwei; Bai, Ge; Zhou, Huihao; Wei, Na; White, Nicholas M.; Lauer, Janelle; Liu, Huaqing; Shi, Yi; Dumitru, Calin Dan; Lettieri, Karen; Shubayev, Veronica; Jordanova, Albena; Guergueltcheva, Velina; Griffin, Patrick R.; Burgess, Robert W.; Pfaff, Samuel L.; Yang, Xiang-Lei

    2015-01-01

    Summary Selective neuronal loss is a hallmark of neurodegenerative diseases, which counter-intuitively are often caused by mutations in widely-expressed genes1. Charcot-Marie-Tooth (CMT) diseases are the most common hereditary peripheral neuropathies, for which there are no effective therapies2,3. A subtype of the diseases—CMT2D—is caused by dominant mutations in GARS, encoding the ubiquitously expressed enzyme glycyl-tRNA synthetase (GlyRS). Despite the broad requirement of GlyRS for protein biosynthesis in all cells, mutations in this gene cause a selective degeneration of peripheral axons leading to deficits in distal motor function4. How mutations in GlyRS (GlyRSCMT2D) are linked to motor neuron vulnerability has remained elusive. Here we report that GlyRSCMT2D acquires a neomorphic binding activity that directly antagonizes an essential signaling pathway for motor neuron survival. We find that CMT2D mutations alter the conformation of GlyRS, enabling GlyRSCMT2D to bind the Neuropilin 1 (Nrp1) receptor. This aberrant interaction competitively interferes with the binding of the cognate ligand vascular endothelial growth factor (VEGF) to Nrp1. Genetic reduction of Nrp1 in mice worsens CMT2D symptoms, whereas enhanced expression of VEGF improves motor function. These findings link the selective pathology of CMT2D to the neomorphic binding activity of GlyRSCMT2D that antagonizes the VEGF/Nrp1 interaction, and indicate the VEGF/Nrp1 signaling axis is an actionable target for treating CMT2D. PMID:26503042

  20. Chemically modified tetracyclines (CMT-3 and CMT-8) enable control of the pathologic remodellation of human aortic valve stenosis via MMP-9 and VEGF inhibition.

    PubMed

    Salo, Tuula; Soini, Ylermi; Oiva, Jani; Kariylitalo; Nissinen, Antti; Biancari, Fausto; Juvonen, Tatu; Satta, Jari

    2006-08-28

    Tetracycline derivatives affect many cellular functions relevant to chronic cardiovascular pathologies, including cell proliferation, migration and matrix remodelling. Accordingly, we sought to determine whether they may modulate the pathologic characteristics known to be significantly involved in human aortic valve stenosis, such as gelatinase production, apoptosis, expression of vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-alpha). The effects of tetracycline derivatives (tetracycline and CMTs-3, -5, -8) on MMP-2 and -9 and their endogenous tissue inhibitor (TIMP-1 and -2) production profiles in explanted human aortic valve pieces were examined by means of gelatine zymography and reverse zymography. Chemiluminescent ELISA was performed to assess VEGF and TNF-alpha concentrations in the medium, and in order to evaluate programmed cell death, in situ labelling of the 3'-ends of the DNA fragments generated by apoptosis-associated endonucleases was performed. CMT-3 and -8 lowered the MMP-9 and VEGF levels significantly in a drug-, dose-, and time-dependent manner. MMP-2 and TIMPs remained unchanged, emphasizing the specificity of CMTs to MMP-9 production on the one hand and restoring the beneficial equilibrium of MMP-9 and TIMPs on the other. Tetracycline was the only drug with a significant impact on net gelatinolytic activity, suggesting that the effect of tetracycline is more extensive concerning total MMP activity. Tetracycline derivatives may have therapeutic effects on the pathologic remodellation of advanced human aortic stenosis through the inhibition of MMP-9 and VEGF production.

  1. Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H).

    PubMed

    Baudot, Cécile; Esteve, Clothilde; Castro, Christel; Poitelon, Yannick; Mas, Camille; Hamadouche, Tarik; El-Rajab, Maryam; Lévy, Nicolas; Megarbané, André; Delague, Valérie

    2012-06-01

    By sequencing of the FGD4 coding sequence in a cohort of 101 patients affected by autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT), we have identified two novel missense mutations in FGD4 in two patients from consanguineous descent: p.Arg442His in an Algerian patient and p.Met566Ile in a Lebanese girl. The patients present early onset, slowly progressive CMT, with drastic reduction of nerve conduction velocities. These mutations are the second and third missense mutations characterized in FGD4. They are likely to lead to conformational changes in the PH1 and FYVE domains. © 2012 Peripheral Nerve Society.

  2. A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N).

    PubMed

    McLaughlin, Heather M; Sakaguchi, Reiko; Giblin, William; Wilson, Thomas E; Biesecker, Leslie; Lupski, James R; Talbot, Kevin; Vance, Jeffery M; Züchner, Stephan; Lee, Yi-Chung; Kennerson, Marina; Hou, Ya-Ming; Nicholson, Garth; Antonellis, Anthony

    2012-01-01

    Charcot-Marie-Tooth (CMT) disease comprises a heterogeneous group of peripheral neuropathies characterized by muscle weakness and wasting, and impaired sensation in the extremities. Four genes encoding an aminoacyl-tRNA synthetase (ARS) have been implicated in CMT disease. ARSs are ubiquitously expressed, essential enzymes that ligate amino acids to cognate tRNA molecules. Recently, a p.Arg329His variant in the alanyl-tRNA synthetase (AARS) gene was found to segregate with dominant axonal CMT type 2N (CMT2N) in two French families; however, the functional consequence of this mutation has not been determined. To investigate the role of AARS in CMT, we performed a mutation screen of the AARS gene in patients with peripheral neuropathy. Our results showed that p.Arg329His AARS also segregated with CMT disease in a large Australian family. Aminoacylation and yeast viability assays showed that p.Arg329His AARS severely reduces enzyme activity. Genotyping analysis indicated that this mutation arose on three distinct haplotypes, and the results of bisulfite sequencing suggested that methylation-mediated deamination of a CpG dinucleotide gives rise to the recurrent p.Arg329His AARS mutation. Together, our data suggest that impaired tRNA charging plays a role in the molecular pathology of CMT2N, and that patients with CMT should be directly tested for the p.Arg329His AARS mutation.

  3. CMT Source Inversions for Massive Data Assimilation in Global Adjoint Tomography

    NASA Astrophysics Data System (ADS)

    Lei, W.; Ruan, Y.; Bozdag, E.; Lefebvre, M. P.; Smith, J. A.; Modrak, R. T.; Komatitsch, D.; Song, X.; Liu, Q.; Tromp, J.; Peter, D. B.

    2015-12-01

    Full Waveform Inversion (FWI) is a vital tool for probing the Earth's interior and enhancing our knowledge of the underlying dynamical processes [e.g., Liu et al., 2012]. Using the adjoint tomography method, we have successfully obtained a first-generation global FWI model named M15 [Bozdag et al., 2015]. To achieve higher resolution of the emerging new structural features and to accommodate azimuthal anisotropy and anelasticity in the next-generation model, we expanded our database from 256 to 4,224 earthquakes. Previous studies have shown that ray-theory-based Centroid Moment Tensor (CMT) inversion algorithms can produce systematic biases in earthquake source parameters due to tradeoffs with 3D crustal and mantle heterogeneity [e.g., Hjorleifsdottir et al., 2010]. To reduce these well-known tradeoffs, we performed CMT inversions in our current 3D global model before resuming the structural inversion with the expanded database. Initial source parameters are selected from the global CMT database [Ekstrom et al., 2012], with moment magnitudes ranging from 5.5 to 7.0 and occurring between 1994 and 2015. Data from global and regional networks were retrieved from the IRIS DMC. Synthetic seismograms were generated based on the spectral-element-based seismic wave propagation solver (SPECFEM3D GLOBE) in model M15. We used a source inversion algorithm based on a waveform misfit function while allowing time shifts between data and synthetics to accommodate additional unmodeled 3D heterogeneity [Liu et al., 2004]. To accommodate the large number of earthquakes and time series (more than 10,000,000 records), we implemented a source inversion workflow based on the newly developed Adaptive Seismic Data Format (ASDF) [Krischer, Smith, et al., 2015] and ObsPy [Krischer et al., 2015]. In ASDF, each earthquake is associated with a single file, thereby eliminating I/O bottlenecks in the workflow and facilitating fast parallel processing. Our preliminary results indicate that errors

  4. Development and Optimization of a Dedicated, Hybrid Dual-Modality SPECT-CmT System for Improved Breast Lesion Diagnosis

    DTIC Science & Technology

    2008-01-01

    Dedicated, Hybrid Dual-Modality SPECT- CmT System for Improved Breast Lesion Diagnosis PRINCIPAL INVESTIGATOR: Priti Madhav...Development and Optimization of a Dedicated, Hybrid Dual-Modality SPECT- CmT System for Improved Breast Lesion Diagnosis 5b. GRANT NUMBER W81XWH-06...implement a dual-modality single photon emission computed tomography (SPECT) and x-ray computed mammotomography ( CmT ) system for the detection and

  5. Fine mapping of de novo CMT1A and HNPP rearrangements within CMT1A-REPs evidences two distinct sex-dependent mechanisms and candidate sequences involved in recombination.

    PubMed

    Lopes, J; Ravisé, N; Vandenberghe, A; Palau, F; Ionasescu, V; Mayer, M; Lévy, N; Wood, N; Tachi, N; Bouche, P; Latour, P; Ruberg, M; Brice, A; LeGuern, E

    1998-01-01

    The molecular mechanism resulting in the duplication or deletion of a 1.5 Mb region of 17p11.2-p12, associated, respectively, with Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), has been proposed to be an unequal crossing-over during meiosis between the two chromosome 17 homologues generated by misalignment of the proximal and distal CMT1A-REP repeats, two homologous sequences flanking the 1.5 Mb CMT1A/HNPP monomer unit. In a recent study of a large series of de novo cases of CMT1A and HNPP, two distinct sex-dependent mechanisms were identified. Rearrangements of paternal origin, essentially duplications, were indeed generated by unequal meiotic crossing-over between the two chromosome 17 homologues, but duplications and deletions of maternal origin resulted from an intrachromosomal process, either unequal sister chromatid exchange or, in the case of deletion, excision of an intrachromatidal loop. In order to determine how these recombinations occur, 24 de novo crossover breakpoints were localized within the 1.7 kb rearrangement hot spot by comparing the sequences of the parental CMT1A-REPs with the chimeric copy in affected offspring. Nineteen out of 21 paternal crossovers were found in a 741 bp hot spot. All the breakpoints of maternal origin (n = 3), however, were located outside this interval, but in closely flanking sequences, supporting the hypothesis that two distinct sex-dependent mechanisms are involved. Several putative recombination promoting sequences in the hot spot, which are rare or absent in the surrounding 7.8 kb, were identified.

  6. P2X7-mediated Increased Intracellular Calcium Causes Functional Derangement in Schwann Cells from Rats with CMT1A Neuropathy*

    PubMed Central

    Nobbio, Lucilla; Sturla, Laura; Fiorese, Fulvia; Usai, Cesare; Basile, Giovanna; Moreschi, Iliana; Benvenuto, Federica; Zocchi, Elena; De Flora, Antonio; Schenone, Angelo; Bruzzone, Santina

    2009-01-01

    Charcot-Marie-Tooth (CMT) is the most frequent inherited neuromuscular disorder, affecting 1 person in 2500. CMT1A, the most common form of CMT, is usually caused by a duplication of chromosome 17p11.2, containing the PMP22 (peripheral myelin protein-22) gene; overexpression of PMP22 in Schwann cells (SC) is believed to cause demyelination, although the underlying pathogenetic mechanisms remain unclear. Here we report an abnormally high basal concentration of intracellular calcium ([Ca2+]i) in SC from CMT1A rats. By the use of specific pharmacological inhibitors and through down-regulation of expression by small interfering RNA, we demonstrate that the high [Ca2+]i is caused by a PMP22-related overexpression of the P2X7 purinoceptor/channel leading to influx of extracellular Ca2+ into CMT1A SC. Correction of the altered [Ca2+]i in CMT1A SC by small interfering RNA or with pharmacological inhibitors of P2X7 restores functional parameters of SC (migration and release of ciliary neurotrophic factor), which are typically defective in CMT1A SC. More significantly, stable down-regulation of the expression of P2X7 restores myelination in co-cultures of CMT1A SC with dorsal root ganglion sensory neurons. These results establish a pathogenetic link between high [Ca2+]i and impaired SC function in CMT1A and identify overexpression of P2X7 as the molecular mechanism underlying both abnormalities. The development of P2X7 inhibitors is expected to provide a new therapeutic strategy for treatment of CMT1A neuropathy. PMID:19546221

  7. Modeling of high-precision wavefront sensing with new generation of CMT avalanche photodiode infrared detectors.

    PubMed

    Gousset, Silvère; Petit, Cyril; Michau, Vincent; Fusco, Thierry; Robert, Clelia

    2015-12-01

    Near-infrared wavefront sensing allows for the enhancement of sky coverage with adaptive optics. The recently developed HgCdTe avalanche photodiode arrays are promising due to their very low detector noise, but still present an imperfect cosmetic that may directly impact real-time wavefront measurements for adaptive optics and thus degrade performance in astronomical applications. We propose here a model of a Shack-Hartmann wavefront measurement in the presence of residual fixed pattern noise and defective pixels. To adjust our models, a fine characterization of such an HgCdTe array, the RAPID sensor, is proposed. The impact of the cosmetic defects on the Shack-Hartmann measurement is assessed through numerical simulations. This study provides both a new insight on the applicability of cadmium mercury telluride (CMT) avalanche photodiodes detectors for astronomical applications and criteria to specify the cosmetic qualities of future arrays.

  8. Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy

    PubMed Central

    Vaccari, Ilaria; Carbone, Antonietta; Previtali, Stefano Carlo; Mironova, Yevgeniya A.; Alberizzi, Valeria; Noseda, Roberta; Rivellini, Cristina; Bianchi, Francesca; Del Carro, Ubaldo; D'Antonio, Maurizio; Lenk, Guy M.; Wrabetz, Lawrence; Giger, Roman J.; Meisler, Miriam H.; Bolino, Alessandra

    2015-01-01

    Mutations of FIG4 are responsible for Yunis-Varón syndrome, familial epilepsy with polymicrogyria, and Charcot-Marie-Tooth type 4J neuropathy (CMT4J). Although loss of the FIG4 phospholipid phosphatase consistently causes decreased PtdIns(3,5)P2 levels, cell-specific sensitivity to partial loss of FIG4 function may differentiate FIG4-associated disorders. CMT4J is an autosomal recessive neuropathy characterized by severe demyelination and axonal loss in human, with both motor and sensory involvement. However, it is unclear whether FIG4 has cell autonomous roles in both motor neurons and Schwann cells, and how loss of FIG4/PtdIns(3,5)P2-mediated functions contribute to the pathogenesis of CMT4J. Here, we report that mice with conditional inactivation of Fig4 in motor neurons display neuronal and axonal degeneration. In contrast, conditional inactivation of Fig4 in Schwann cells causes demyelination and defects in autophagy-mediated degradation. Moreover, Fig4-regulated endolysosomal trafficking in Schwann cells is essential for myelin biogenesis during development and for proper regeneration/remyelination after injury. Our data suggest that impaired endolysosomal trafficking in both motor neurons and Schwann cells contributes to CMT4J neuropathy. PMID:25187576

  9. A novel NDRG1 mutation in a non-Romani patient with CMT4D/HMSN-Lom.

    PubMed

    Piscosquito, Giuseppe; Magri, Stefania; Saveri, Paola; Milani, Micaela; Ciano, Claudia; Farina, Laura; Taroni, Franco; Pareyson, Davide

    2017-03-01

    Charcot-Marie-Tooth disease type 4D (CMT4D), also known as hereditary motor and sensory neuropathy Lom type (HMSNL), is an autosomal recessive, early onset, severe demyelinating neuropathy with hearing loss, caused by N-Myc downstream-regulated gene 1 (NDRG1) mutations. CMT4D is rare with only three known mutations, one of which (p.Arg148Ter) is found in patients of Romani ancestry and accounts for the vast majority of cases. We report a 38-year-old Italian female with motor development delay, progressive neuropathy, and sensorineural deafness. Magnetic resonance imaging showed slight atrophy of cerebellum, medulla oblongata, and upper cervical spinal cord. She had a novel homozygous NDRG1 frameshift mutation (c.739delC; p.His247ThrfsTer74). The identification of this NDRG1 mutation confirms that CMT4D is not a private Romani disease and should be considered in the differential diagnosis of recessive demyelinating CMT.

  10. The antiprogestins mifepristone and onapristone reduce cell proliferation in the canine mammary carcinoma cell line CMT-U27.

    PubMed

    Guil-Luna, Silvia; Hellmén, Eva; Sánchez-Céspedes, Raquel; Millán, Yolanda; Martín de las Mulas, Juana

    2014-07-01

    Canine mammary tumours (CMTs) represent nearly half of all tumours in female dogs and some 50% have malignant behaviour. Simple epithelial carcinomas have shorter disease free periods after surgery and a higher reduction of the proliferation index reduction after antiprogestin aglepristone treatment in vivo related to the expression of progesterone receptors (PR). These findings make simple carcinomas good candidates for endocrine therapy. To further explore this possibility, the effects of the antiprogestins mifepristone (RU486) and onapristone (ZK299) on cell viability and PR expression of the canine mammary carcinoma cell line isolated from a simple epithelial carcinoma CMT-U27 were studied. Twenty five percent of CMT-U27 control cells expressed PR. RU486 (p<0.05) and ZK299 (p<0.05) reduced the number of viable cells (WST-8 test) at 24h but only the latter treatment reduced significantly PR expression in viable tumour cells at 24h of incubation. The results suggest that both RU486 and ZK299 induce a decrease in the number of viable CMT-U27 tumour cells with different effects on PR expression. The canine mammary carcinoma cell line CMT-U27 is sensitive to the effects of antiprogestins and may serve to further explore the role of these drugs in canine mammary carcinomas.

  11. Application of the CMT algorithm to analog recordings of deep earthquakes

    NASA Astrophysics Data System (ADS)

    Huang, Wei-Chuang; Ekström, Göran; Okal, Emile A.; Salganik, Mikhail P.

    1994-06-01

    The distribution and characteristics of deep earthquakes provide important information on both the large-scale aspects of mantle convection as well as on the small-scale mechanics of apparent shear failure within descending lithospheric plates at large confining pressures. Neither of these processes is well understood, but the detailed knowledge of the spatial and temporal distribution of earthquakes, as well as the focal geometries, scalar moments, and details of the earthquake rupture process, provides constraints which can be used to differentiate between competing models of mantle circulation and theories of deep seismic rupture. With the objective of expanding and improving the database of source parameters for deep earthquakes, we evaluate the feasibility of applying the Harvard centroid moment tensor (CMT) algorithm to earlier (pre-1977) earthquakes recorded on seismographs with analog recording. Abundant records from the World Wide Standardized Seismograph Network (WWSSN) are available for events after 1962, and the data from these high-quality stations with a known standard response are easily digitized and subjected to analysis by the CMT algorithm. For earlier events, no standardized network of seismometers is available. Using a modem deep earthquake as a test case, we show that reliable single-station moment tensor solutions can be obtained from the Press-Ewing instrument at Pasadena. We apply the single-station technique to three historical earthquakes recorded on different types of electromagnetic and mechanical seismographs: the 1957 Java earthquake (Press-Ewing); the 1922 Peru earthquake (Wiechert); and the 1911 Peru-Brazil earthquake (Galitzin). Robust results can be achieved from these data provided the instruments are well calibrated, and an analysis of selected earlier deep earthquakes may quickly double or triple the time span of the database of deep earthquake source parameters.

  12. Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT

    PubMed Central

    Tomaselli, Pedro J.; Rossor, Alexander M.; Horga, Alejandro; Jaunmuktane, Zane; Carr, Aisling; Saveri, Paola; Piscosquito, Giuseppe; Pareyson, Davide; Laura, Matilde; Blake, Julian C.; Poh, Roy; Polke, James; Houlden, Henry

    2017-01-01

    Objective: To determine the prevalence and clinical and genetic characteristics of patients with X-linked Charcot-Marie-Tooth disease (CMT) due to mutations in noncoding regions of the gap junction β-1 gene (GJB1). Methods: Mutations were identified by bidirectional Sanger sequence analysis of the 595 bases of the upstream promoter region, and 25 bases of the 3′ untranslated region (UTR) sequence in patients in whom mutations in the coding region had been excluded. Clinical and neurophysiologic data were retrospectively collected. Results: Five mutations were detected in 25 individuals from 10 kindreds representing 11.4% of all cases of CMTX1 diagnosed in our neurogenetics laboratory between 1996 and 2016. Four pathogenic mutations, c.-17G>A, c.-17+1G>T, c.-103C>T, and c.-146-90_146-89insT were detected in the 5′UTR. A novel mutation, c.*15C>T, was detected in the 3′ UTR of GJB1 in 2 unrelated families with CMTX1 and is the first pathogenic mutation in the 3′UTR of any myelin-associated CMT gene. Mutations segregated with the phenotype, were at sites predicted to be pathogenic, and were not present in the normal population. Conclusions: Mutations in noncoding DNA are a major cause of CMTX1 and highlight the importance of mutations in noncoding DNA in human disease. Next-generation sequencing platforms for use in inherited neuropathy should therefore include coverage of these regions. PMID:28283593

  13. Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT.

    PubMed

    Tomaselli, Pedro J; Rossor, Alexander M; Horga, Alejandro; Jaunmuktane, Zane; Carr, Aisling; Saveri, Paola; Piscosquito, Giuseppe; Pareyson, Davide; Laura, Matilde; Blake, Julian C; Poh, Roy; Polke, James; Houlden, Henry; Reilly, Mary M

    2017-04-11

    To determine the prevalence and clinical and genetic characteristics of patients with X-linked Charcot-Marie-Tooth disease (CMT) due to mutations in noncoding regions of the gap junction β-1 gene (GJB1). Mutations were identified by bidirectional Sanger sequence analysis of the 595 bases of the upstream promoter region, and 25 bases of the 3' untranslated region (UTR) sequence in patients in whom mutations in the coding region had been excluded. Clinical and neurophysiologic data were retrospectively collected. Five mutations were detected in 25 individuals from 10 kindreds representing 11.4% of all cases of CMTX1 diagnosed in our neurogenetics laboratory between 1996 and 2016. Four pathogenic mutations, c.-17G>A, c.-17+1G>T, c.-103C>T, and c.-146-90_146-89insT were detected in the 5'UTR. A novel mutation, c.*15C>T, was detected in the 3' UTR of GJB1 in 2 unrelated families with CMTX1 and is the first pathogenic mutation in the 3'UTR of any myelin-associated CMT gene. Mutations segregated with the phenotype, were at sites predicted to be pathogenic, and were not present in the normal population. Mutations in noncoding DNA are a major cause of CMTX1 and highlight the importance of mutations in noncoding DNA in human disease. Next-generation sequencing platforms for use in inherited neuropathy should therefore include coverage of these regions. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  14. Fate of Schwann cells in CMT1A and HNPP: evidence for apoptosis.

    PubMed

    Erdem, S; Mendell, J R; Sahenk, Z

    1998-06-01

    The fate of Schwann cells in Charcot-Marie-Tooth (CMT) neuropathies was addressed in this study of nerve biopsies from patients with proven PMP22 duplications and deletions. In frozen sections, apoptotic nuclei were detected using the TUNEL method. In adjacent sections, anti-neurofilament 68kD antibody was used as an axonal marker, while the antibodies to NKH-1 and low-affinity nerve growth factor receptor P75NTR were used as Schwann cell markers. In addition, plastic sections were used to determine the densities of myelinated fibers and Schwann cell nuclei. In all biopsies from CMT1A, TUNEL-positive nuclei appeared in clusters. In adjacent sections, areas of TUNEL-positive nuclei matched with areas devoid of neurofilaments and NKH-1-positive Schwann cell silhouettes, suggesting that the apoptotic nuclei belonged to nonmyelinating Schwann cells. In addition, quantitative studies on plastic-embedded sections showed a significantly reduced number of total Schwann cells compared with controls, strongly favoring a loss of Schwann cell by apoptosis. In HNPP, the number of total Schwann cells was increased and a significant Schwann cell apoptosis was observed in only 2 patients. Examination of plastic sections and teased nerve preparations from these cases suggested that the Schwann cell apoptosis might be related to the regenerative state of the nerve resulting from the process of sprout pruning. No strict correlation between p75NTR expression and apoptosis was found. These studies indicate that factors regulating Schwann cell number in early postnatal development continue to be important for Schwann cell survival throughout life.

  15. Potato dextrose agar antifungal susceptibility testing for yeasts and molds: evaluation of phosphate effect on antifungal activity of CMT-3.

    PubMed

    Liu, Yu; Tortora, George; Ryan, Maria E; Lee, Hsi-Ming; Golub, Lorne M

    2002-05-01

    The broth macrodilution method (BMM) for antifungal susceptibility testing, approved by the National Committee for Clinical Laboratory Standards (NCCLS), was found to have deficiencies in testing of the antifungal activity of a new type of antifungal agent, a nonantibacterial chemically modified tetracycline (CMT-3). The high content of phosphate in the medium was found to greatly increase the MICs of CMT-3. To avoid the interference of phosphate in the test, a new method using potato dextrose agar (PDA) as a culture medium was developed. Eight strains of fungi, including five American Type Culture Collection strains and three clinical isolates, were used to determine the MICs of amphotericin B and itraconazole with both the BMM and the PDA methods. The MICs of the two antifungal agents determined with the PDA method showed 99% agreement with those determined with the BMM method within 1 log(2) dilution. Similarly, the overall reproducibility of the MICs with the PDA method was above 97%. Three other antifungal agents, fluconazole, ketoconazole, and CMT-3, were also tested in parallel against yeasts and molds with both the BMM and the PDA methods. The MICs of fluconazole and ketoconazole determined with the PDA method showed 100% agreement within 1 log(2) dilution of those obtained with the BMM method. However, the MICs of CMT-3 determined with the BMM method were as high as 128 times those determined with the PDA method. The effect of phosphate on the antifungal activity of CMT-3 was evaluated by adding Na2HPO4 to PDA in the new method. It was found that the MIC of CMT-3 against a Penicillium sp. increased from 0.5 microg/ml (control) to 2.0 microg/ml when the added phosphate was used at a concentration of 0.8 mg/ml, indicating a strong interference of Na2HPO4 with the antifungal activity of CMT-3. Except for fluconazole, all the other antifungal agents demonstrated clear end points among the yeasts and molds tested. Nevertheless, with its high reproducibility

  16. The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases.

    PubMed

    Sinkiewicz-Darol, Elena; Lacerda, Andressa Ferreira; Kostera-Pruszczyk, Anna; Potulska-Chromik, Anna; Sokołowska, Beata; Kabzińska, Dagmara; Brunetti, Craig R; Hausmanowa-Petrusewicz, Irena; Kochański, Andrzej

    2015-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified. We decided to explore if the LITAF/SIMPLE gene shared a functional link to the PMP22 gene, whose duplication or deletion results in CMT1A and HNPP, respectively. By studying a large cohort of CMT1A/HNPP-affected patients, we found that the LITAF I92V sequence variant predisposes patients to an earlier age of onset of both the CMT1A and HNPP diseases. Using cell transfection experiments, we showed that the LITAF I92V sequence variant partially mislocalizes to the mitochondria in contrast to wild-type LITAF which localizes to the late endosome/lysosomes and is associated with a tendency for PMP22 to accumulate in the cells. Overall, this study shows that the I92V LITAF sequence variant would be a good candidate for a biomarker in the case of the CMT1A/HNPP disorders.

  17. Synergistic growth inhibitory effect of deracoxib with doxorubicin against a canine mammary tumor cell line, CMT-U27

    PubMed Central

    BAKIREL, Tülay; ALKAN, Fulya Üstün; ÜSTÜNER, Oya; ÇINAR, Suzan; YILDIRIM, Funda; ERTEN, Gaye; BAKIREL, Utku

    2016-01-01

    Cyclooxygenase (COX) inhibitors have been shown to exert anti-angiogenic and anti-tumor activities on many types of malignant tumors. These anticancer properties make it worthwhile to examine the possible benefit of combining COX inhibitors with other anti-cancer agents. In the present study, we evaluated the potential of deracoxib (DER) in potentiating antitumor activity of doxorubicin (DOX) in canine mammary carcinoma cells (CMT-U27). DER (50–250 µM) enhanced the antiproliferative activity of DOX by reducing the IC50 (approximately 3- to 3.5 fold). Interaction analysis of the data showed that combinations of DOX at 0.9 µM with DER (100–250 µM) produced synergism in the CMT-U27 cell line, with a ratio index ranging from 1.98 to 2.33. In additional studies identifying the mechanism of observed synergistic effect, we found that DER strongly potentiated DOX-caused G0/G1 arrest in cell cycle progression. Also, DER (100–250 µM) augmented apoptosis induction with approximately 1.35- and 1.37- fold increases in apoptotic response caused by DOX in the cells. DER enhanced the antiproliferative effect of DOX in conjunction with induction of apoptosis by modulation of Bcl-2 expression and changes in the cell cycle of the CMT-U27 cell line. Although the exact molecular mechanism of the alterations in the cell cycle and apoptosis observed with DER and DOX combinations require further investigations, the results suggest that the synergistic effect of DOX and DER combinations in CMT therapy may be achieved at relatively lower doses of DOX with lesser side effects. Therefore, combining DER with DOX may prove beneficial in the clinical treatment of canine mammary cancer. PMID:26822118

  18. Synergistic growth inhibitory effect of deracoxib with doxorubicin against a canine mammary tumor cell line, CMT-U27.

    PubMed

    Bakirel, Tülay; Alkan, Fulya Üstün; Üstüner, Oya; Çinar, Suzan; Yildirim, Funda; Erten, Gaye; Bakirel, Utku

    2016-05-03

    Cyclooxygenase (COX) inhibitors have been shown to exert anti-angiogenic and anti-tumor activities on many types of malignant tumors. These anticancer properties make it worthwhile to examine the possible benefit of combining COX inhibitors with other anti-cancer agents. In the present study, we evaluated the potential of deracoxib (DER) in potentiating antitumor activity of doxorubicin (DOX) in canine mammary carcinoma cells (CMT-U27). DER (50-250 µM) enhanced the antiproliferative activity of DOX by reducing the IC50 (approximately 3- to 3.5 fold). Interaction analysis of the data showed that combinations of DOX at 0.9 µM with DER (100-250 µM) produced synergism in the CMT-U27 cell line, with a ratio index ranging from 1.98 to 2.33. In additional studies identifying the mechanism of observed synergistic effect, we found that DER strongly potentiated DOX-caused G0/G1 arrest in cell cycle progression. Also, DER (100-250 µM) augmented apoptosis induction with approximately 1.35- and 1.37- fold increases in apoptotic response caused by DOX in the cells. DER enhanced the antiproliferative effect of DOX in conjunction with induction of apoptosis by modulation of Bcl-2 expression and changes in the cell cycle of the CMT-U27 cell line. Although the exact molecular mechanism of the alterations in the cell cycle and apoptosis observed with DER and DOX combinations require further investigations, the results suggest that the synergistic effect of DOX and DER combinations in CMT therapy may be achieved at relatively lower doses of DOX with lesser side effects. Therefore, combining DER with DOX may prove beneficial in the clinical treatment of canine mammary cancer.

  19. Drosophila as a platform to predict the pathogenicity of novel aminoacyl-tRNA synthetase mutations in CMT.

    PubMed

    Leitão-Gonçalves, Ricardo; Ermanoska, Biljana; Jacobs, An; De Vriendt, Els; Timmerman, Vincent; Lupski, James R; Callaerts, Patrick; Jordanova, Albena

    2012-05-01

    Charcot-Marie-Tooth disease (CMT) is the major form of inherited peripheral neuropathy in humans. CMT is clinically and genetically heterogeneous and four aminoacyl-tRNA synthetases have been implicated in disease etiology. Mutations in the YARS gene encoding a tyrosyl-tRNA synthetase (TyrRS) lead to Dominant Intermediate CMT type C (DI-CMTC). Three dominant YARS mutations were so far associated with DI-CMTC. To further expand the spectrum of CMT causing genetic defects in this tRNA synthetase, we performed DNA sequencing of YARS coding regions in a cohort of 181 patients with various types of peripheral neuropathy. We identified a novel K265N substitution that in contrast to all previously described mutations is located at the anticodon recognition domain of the enzyme. Further genetic analysis revealed that this variant represents a benign substitution. Using our recently developed DI-CMTC Drosophila model, we tested in vivo the pathogenicity of this new YARS variant. We demonstrated that the developmental and behavioral defects induced by all DI-CMTC causing mutations were not present upon ubiquitous or panneuronal TyrRS K265N expression. Thus, in line with our genetic studies, functional analysis confirmed that the K265N substitution does not induce toxicity signs in Drosophila. The consistency observed throughout this work underscores the robustness of our DI-CMTC animal model and identifies Drosophila as a valid read-out platform to ascertain the pathogenicity of novel mutations to be identified in the future.

  20. SNM Movement Detection/Radiation Sensors and Advanced Materials Portfolio Review, CdMnTe (CMT) Gamma Ray Detectors

    SciTech Connect

    Bolotnikov,A.

    2009-06-02

    The project goals are: (1) Develop CMT radiation detectors - Demonstrate feasibility (Phase 1 is complete) and Improve material properties and device performance; (2) This project will lead to novel radiation detectors - high detection efficiency, high energy-resolution, ambient-temperature operation, and low production cost; and (3) Such detectors are needed in areas of nonproliferation and national security for detection of SNM. Research highlights are: (1) We achieved our Phase-I goal - Demonstration of CMT detector performance approaching that of CZT detectors; (2) Demonstrated that In-doped CMT is much closer to its anticipated performance as radiation detectors than other alternative materials, TlBr and HgI{sub 2} - Large crystal volumes, 10{sup 10}{Omega}{center_dot}cm, 3 x 10{sup -3}cm{sup 2}/V, and stable response; and (3) Conducted material and device characterization experiments - Detectors: I-V, {mu}{sub e}, ({mu}{tau}){sub e}, internal E fields, energy spectra, and high-resolution x-ray response mapping data and Materials - DLTS, TCT, PL, EPDs, XRD, PCD and IR transmission.

  1. CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene.

    PubMed

    Chen, D-H; Sul, Y; Weiss, M; Hillel, A; Lipe, H; Wolff, J; Matsushita, M; Raskind, W; Bird, T

    2010-11-30

    Recently, mutations in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4) have been reported in Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in this same gene have been described in separate families with various skeletal dysplasias. Further clarification is needed of the different phenotypes associated with this gene. We performed clinical evaluation, electrophysiology, and genetic analysis of the TRPV4 gene in 2 families with CMT2C. Two multigenerational families had a motor greater than sensory axonal neuropathy associated with variable vocal cord paresis. The vocal cord paresis varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One family with mild neuropathy also manifested pronounced short stature, more than 2 SD below the average height for white Americans. There was one instance of dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this family. The other family had a more severe, progressive, motor neuropathy with sensory loss, but less remarkable short stature and an R315W mutation in TRPV4. Third cranial nerve involvement and sleep apnea occurred in one subject in each family. CMT2C with axonal neuropathy, vocal cord paresis, and short stature is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result in highly variable orthopedic and neurologic phenotypes.

  2. Assessement of quadriceps strength, endurance and fatigue in FSHD and CMT: benefits and limits of femoral nerve magnetic stimulation.

    PubMed

    Bachasson, D; Temesi, J; Bankole, C; Lagrange, E; Boutte, C; Millet, G Y; Verges, S; Levy, P; Feasson, L; Wuyam, B

    2014-02-01

    To (i) evaluate the feasibility and the reliability of a test assessing quadriceps strength, endurance and fatigue in patients with fascioscapulohumeral dystrophy (FSHD) and Charcot-Marie-Tooth disease (CMT), (ii) compare quadriceps function between patients and healthy controls. Controls performed the test once and patients twice on two separate visits. It involved progressive sets of 10 isometric contractions each followed by neuromuscular assessments with FNMS. Volitional assessment of muscle strength, endurance and fatigue appeared to be reliable in FSHD and CMT patients. Supramaximal FNMS was achieved in ∼70% of FSHD patients and in no CMT patients. In FSHD patients, Femoral nerve magnetic stimulation (FNMS) provided reliable assessment of central (typical error as a coefficient of variation (CVTE)<8% for voluntary activation) and peripheral (CVTE<10% and intraclass coefficient correlation >0.85 for evoked responses) function. Patients and controls had similar reductions in evoked quadriceps responses, voluntary activation and similar endurance. This test provides reliable evaluation but FNMS exhibits limitations due to insufficient stimulation intensity particularly in neurogenic conditions. It showed similar central and peripheral quadriceps fatigability in patients and controls. This test may be a valuable tool for patient follow-up although further development of magnetic stimulation devices is needed to extend its applicability. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Application of whole-exome sequencing for detecting copy number variants in CMT1A/HNPP.

    PubMed

    Jo, H-Y; Park, M-H; Woo, H-M; Han, M H; Kim, B-Y; Choi, B-O; Chung, K W; Koo, S K

    2016-08-01

    Large insertions and deletions (indels), including copy number variations (CNVs), are commonly seen in many diseases. Standard approaches for indel detection rely on well-established methods such as qPCR or short tandem repeat (STR) markers. Recently, a number of tools for CNV detection based on next-generation sequencing (NGS) data have also been developed; however, use of these methods is limited. Here, we used whole-exome sequencing (WES) in patients previously diagnosed with CMT1A or HNPP using STR markers to evaluate the ability of WES to improve the clinical diagnosis. Patients were evaluated utilizing three CNV detection tools including CONIFER, ExomeCNV and CEQer, and array comparative genomic hybridization (aCGH). We identified a breakpoint region at 17p11.2-p12 in patients with CMT1A and HNPP. CNV detection levels were similar in both 6 Gb (mean read depth = 80×) and 17 Gb (mean read depth = 190×) data. Taken together, these data suggest that 6 Gb WES data are sufficient to reveal the genetic causes of various diseases and can be used to estimate single mutations, indels, and CNVs simultaneously. Furthermore, our data strongly indicate that CNV detection by NGS is a rapid and cost-effective method for clinical diagnosis of genetically heterogeneous disorders such as CMT neuropathy.

  4. Quantification of soil heterogeneity induced by corroding metal objects, using X-ray computed micro tomography (CMT)

    NASA Astrophysics Data System (ADS)

    Afanasyev, Michael; Heimovaara, Timo; van Paassen, Leon

    2014-05-01

    Metal objects in soil, such as pipelines and sheet pile walls are subject to corrosion, that causes extensive economic damage - the annual direct costs of metal corrosion are estimated as 3-4% of the gross domestic product (GDP) of both developed and developing countries. Corrosion of the metal object results in the diffusion of corrosion products away from the original metal surface, where the corrosion products combine with dissolved species and precipitate, altering the properties of the porous medium. The result is a system composed of the uncorroded metal, the Dense Product Layer (DPL) composed of iron corrosion products, the Transformed Medium (TM) which is a mix of the corrosion products and compounds coming from the surrounding soil and the unaltered soil. Naturally occurring DPL's were reported to reduce the corrosion rate of metal objects in soil and studies of metal archaeological artifacts show that it is possible that microbiota plays a role in the process, controlling the rate and location of reprecipitation of corrosion products. However, the dynamics of such complex processes in soil are not yet fully understood and experimental results that can be used to calibrate and verify numerical models of corrosion processes in porous media are scarce. In this study, we explore the potential of X-ray computed microtomography (CMT) in quantifying the changes occurring in soil around corroding metal objects. Metal coupons were incubated in sand and scanned using a Phoenix Nanotom® s nanofocus computed tomography system. Using objects of known density in the samples, the measurements were density-calibrated and the increase in density and accompanying reduction in porosity due to reprecipitation of corrosion products were quantified. Our results demonstrate the potential of X-ray tomography in non-destructive quantification of corrosion processes in porous media. We suggest using smaller samples to increase resolution of the measurements and to use

  5. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients.

    PubMed

    Mannil, Manoj; Solari, Alessandra; Leha, Andreas; Pelayo-Negro, Ana L; Berciano, José; Schlotter-Weigel, Beate; Walter, Maggie C; Rautenstrauss, Bernd; Schnizer, Tuuli J; Schenone, Angelo; Seeman, Pavel; Kadian, Chandini; Schreiber, Olivia; Angarita, Natalia G; Fabrizi, Gian Maria; Gemignani, Franco; Padua, Luca; Santoro, Lucio; Quattrone, Aldo; Vita, Giuseppe; Calabrese, Daniela; Young, Peter; Laurà, Matilde; Haberlová, Jana; Mazanec, Radim; Paulus, Walter; Beissbarth, Tim; Shy, Michael E; Reilly, Mary M; Pareyson, Davide; Sereda, Michael W

    2014-11-01

    This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures - the 10m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry - further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials.

  6. Isolation of novel genes from the CMT1A duplication/HNPP deletion critical region in 17p11.2-p12.

    PubMed

    Murakami, T; Sun, Z S; Lee, C C; Lupski, J R

    1997-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem DNA duplication in chromosome 17p11.2-p12, while hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this locus. The 1.5-Mb CMT1A monomer unit duplicated in CMT1A and deleted in HNPP is flanked by low-copy repeats termed CMT1A-REPs. Both diseases appear to be caused by an altered copy number of the peripheral myelin protein 22 gene (PMP22), which lies within the critical region. To identify additional genes rapidly, we used a cosmid contig of this region and reciprocal probing of arrayed chromosome 17-specific cosmid and cDNA libraries. Three cDNA clones were identified within the CMT1A duplication/HNPP deletion region and one just proximal to the critical region. The cDNA for human heme A:farnesyltransferase (COX10) mapped 10 kb centromeric to the distal CMT1A-REP. The other two cDNA clones from within the critical interval mapped to cosmid 126D1 at the mfd41 (D17S261) DNA marker, and their conceptual translation showed homology to 60S ribosomal protein L9 (RPL9) and chromosomal protein RMSA-1 (RMSA-1). A gene that is homologous to human peroxisome proliferator activated receptor alpha (hPPARA) was identified near the proximal CMT1A-REP.

  7. In vivo selection of a complex mutant TEM (CMT) from an inhibitor-resistant TEM (IRT) during ceftazidime therapy.

    PubMed

    Jacquier, H; Marcadé, G; Raffoux, E; Dombret, H; Woerther, P L; Donay, J L; Arlet, G; Cambau, E

    2013-12-01

    A relapse from Escherichia coli bloodstream infection was observed in a patient with acute leukaemia treated with ceftazidime for 7 days for febrile neutropenia. Whereas the original E. coli isolate was resistant to β-lactam/β-lactamase inhibitor combinations (EC1), the relapse E. coli isolate showed a similar phenotype but with resistance extended to ceftazidime (EC2). We investigated the molecular mechanisms of β-lactam resistance and sought if EC2 could have been selected in vivo from EC1. EC1 and EC2 isolates were compared for antibiotic MICs, plasmid content, genotyping, β-lactamase genes and their environment. Both isolates were conjugated with E. coli JW4111ΔampC and MICs determined for transconjugants. In addition, ceftazidime-resistant mutants were selected in vitro from EC1. EC1 and EC2 showed identical patterns for genotyping and resistance plasmids. PCR sequencing of blaTEM in EC1 showed the mutations M69L and N276D corresponding to TEM-35, also called inhibitor-resistant TEM (IRT)-4. In EC2, the TEM allele showed an additional mutation, R164S, known to confer resistance to ceftazidime. The combination of these three mutations was previously reported in TEM-158, described as the complex mutant TEM (CMT)-9, associated with resistance to β-lactamase inhibitors and third-generation cephalosporins. In vitro selection of ceftazidime-resistant mutants from EC1 yielded six different CMT alleles, including TEM-158 containing the R164S mutation. This first known report of in vivo selection of CMT from IRT, reproduced in vitro, shows how the evolution of β-lactamase enzymes is easily driven by antibiotic pressure, even during a short antibiotic therapy.

  8. Genotypes & sensory phenotypes in 2 new X-linked neuropathies (CMTX3 and dSMAX) and dominant CMT/HMN overlap syndromes.

    PubMed

    Nicholson, Garth; Kennerson, Marina; Brewer, Megan; Garbern, James; Shy, Michael

    2009-01-01

    Classification of neuropathies into Charcot-Marie-Tooth syndrome (CMT, hereditary motor and sensory neuropathy) or purely motor neuropathies is relatively easy in single patients but subtle sensory findings can vary in different affected individuals in a family. We examined the extent of sensory involvement in different individuals in two new X-linked neuropathy syndromes (CMTX3 and dSMAX) and in some dominantly inherited mainly motor neuropathies. CMTX3 is a mild X- linked recessive CMT phenotype linked to Xq26-28. dSMAX (distal spinal muscular atrophy linked to Xq13-21). We describe a new family linked to this locus that has some sensory findings which could also be described as a motor and sensory neuropathy i.e. a form of CMT. In our dominant distal hereditary motor neuropathy (HMN) family linked to chromosome 7 (dHMN1) we also found some affected individuals with sensory signs as well as reduced sensory action potentials. In reported HMN families with known mutations in GARS, SETX, HSPB1 and HSPB8 genes and in many of our HMN families with unknown gene mutations, there is sensory involvement producing a CMT phenotype in some individuals. These disorders do not easily fit into traditional hereditary neuropathy classifications and should be recognised as CMT/HMN overlap syndromes. Recognition of overlap syndromes may assist development of more accurate gene screening paradigms.

  9. Screening of the 17p11.2--p12 region in a large cohort of patients with Charcot-Marie-Tooth (CMT) disease or hereditary neuropathy with liability to pressure palsies (HNPP).

    PubMed

    Kabzinska, D; Pierscinska, J; Kochanski, A

    2009-01-01

    Within the last decade, numerous methods have been applied to detect the most common mutation in patients affected with Charcot-Marie-Tooth (CMT) disease, i.e. submicroscopic duplication in the 17p11.2--p12 region. In 1993, another neuropathy - known as hereditary neuropathy with liability to pressure palsies (HNPP) - has been shown to be caused by a 17p11.2--p12 deletion. Historically, Southern blot analysis was the first approach to identify CMT1A duplication or HNPP deletion. This time- and labor-consuming method requires prior selection of DNA samples. In fact, only CMT patients affected with the demyelinating form of CMT1 have been screened for CMT1A duplication. After the 17p11.2--p12 duplication was identified in the CMT1 families, subsequent studies revealed additional axonal features in the patients harboring the 17p11.2--p12 duplication. Thus it seems reasonable to test all patients affected with CMT for the presence of the 17p11.2--p12 duplication. To evaluate the utility of real-time polymerase chain reaction (Q-PCR) and restriction fragment length polymorphism PCR (RFLP-PCR), we screened a large group of 179 families with the diagnosis of CMT/HNPP for the presence of the 17p11.2--p12 duplication/deletion. Due to a high frequency of CMT1A duplication in familial cases of CMT, we propose (in contrast to the previous studies) to perform Q-PCR analysis in all patients diagnosed with CMT.

  10. Radiosynthesis and validation of 18F-FP-CMT, a phenyltropane with superior properties for imaging the dopamine transporter in living brain

    PubMed Central

    Cumming, Paul; Maschauer, Simone; Riss, Patrick J; Tschammer, Nuska; Fehler, Stefanie K; Heinrich, Markus R; Kuwert, Torsten; Prante, Olaf

    2014-01-01

    To date there is no validated, 18F-labeled dopamine transporter (DAT) radiotracer with a rapid kinetic profile suitable for preclinical small-animal positron emission tomography (PET) studies in rodent models of human basal ganglia disease. Herein we report radiosynthesis and validation of the phenyltropane 18F-FP-CMT. Dynamic PET recordings were obtained for 18F-FP-CMT in six untreated rats, and six rats pretreated with the high-affinity DAT ligand GBR 12909; mean parametric maps of binding potential (BPND) relative to the cerebellum reference region, and maps of total distribution volume (VT) relative to the metabolite-corrected arterial input were produced. 18F-FP-CMT BPND maps showed peak values of ∼4 in the striatum, versus ∼0.4 in the vicinity of the substantia nigra. Successive truncation of the PET recordings indicated that stable BPND estimates could be obtained with recordings lasting only 45 minutes, reflecting rapid kinetics of 18F-FP-CMT. Pretreatment with GBR 12909 reduced the striatal binding by 72% to 76%. High-performance liquid chromatography analysis revealed rapid metabolism of 18F-FP-CMT to a single, non-brain penetrant hydrophilic metabolite. Total distribution of volume calculated relative to the metabolite-corrected arterial input was 4.4 mL/g in the cerebellum. The pharmacological selectivity of 18F-FP-CMT, rapid kinetic profile, and lack of problematic metabolites constitute optimal properties for quantitation of DAT in rat, and may also predict applicability in human PET studies. PMID:24714035

  11. Radiosynthesis and validation of ¹⁸F-FP-CMT, a phenyltropane with superior properties for imaging the dopamine transporter in living brain.

    PubMed

    Cumming, Paul; Maschauer, Simone; Riss, Patrick J; Tschammer, Nuska; Fehler, Stefanie K; Heinrich, Markus R; Kuwert, Torsten; Prante, Olaf

    2014-07-01

    To date there is no validated, (18)F-labeled dopamine transporter (DAT) radiotracer with a rapid kinetic profile suitable for preclinical small-animal positron emission tomography (PET) studies in rodent models of human basal ganglia disease. Herein we report radiosynthesis and validation of the phenyltropane (18)F-FP-CMT. Dynamic PET recordings were obtained for (18)F-FP-CMT in six untreated rats, and six rats pretreated with the high-affinity DAT ligand GBR 12909; mean parametric maps of binding potential (BPND) relative to the cerebellum reference region, and maps of total distribution volume (VT) relative to the metabolite-corrected arterial input were produced. (18)F-FP-CMT BPND maps showed peak values of ∼4 in the striatum, versus ∼0.4 in the vicinity of the substantia nigra. Successive truncation of the PET recordings indicated that stable BPND estimates could be obtained with recordings lasting only 45 minutes, reflecting rapid kinetics of (18)F-FP-CMT. Pretreatment with GBR 12909 reduced the striatal binding by 72% to 76%. High-performance liquid chromatography analysis revealed rapid metabolism of (18)F-FP-CMT to a single, non-brain penetrant hydrophilic metabolite. Total distribution of volume calculated relative to the metabolite-corrected arterial input was 4.4 mL/g in the cerebellum. The pharmacological selectivity of (18)F-FP-CMT, rapid kinetic profile, and lack of problematic metabolites constitute optimal properties for quantitation of DAT in rat, and may also predict applicability in human PET studies.

  12. Near Real-time Full-wave Centroid Moment Tensor (CMT) Inversion for Ground-motion forecast in 3D Earth Structure of Southern California

    NASA Astrophysics Data System (ADS)

    Chen, P.; Lee, E.; Jordan, T. H.; Maechling, P. J.

    2011-12-01

    Accurate and rapid CMT inversion is important for seismic hazard analysis. We have developed an algorithm for very rapid full-wave CMT inversions in a 3D Earth structure model and applied it on earthquakes recorded by the Southern California Seismic Network (SCSN). The procedure relies on the use of receiver-side Green tensors (RGTs), which comprise the spatial-temporal displacements produced by the three orthogonal unit impulsive point forces acting at the receiver. We have constructed a RGT database for 219 broadband stations in Southern California using an updated version of the 3D SCEC Community Velocity Model (CVM) version 4.0 and a staggered-grid finite-difference code. Finite-difference synthetic seismograms for any earthquake in our modeling volume can be simply calculated by extracting a small, source-centered volume from the RGT database and applying the reciprocity principle. We have developed an automated algorithm that combines a grid-search for suitable epicenter and focal mechanisms with a gradient-descent method that further refines the grid-search results. In this algorithm, the CMT solutions are inverted near real-time by using waveform in a 3D Earth structure. Comparing with the CMT solutions provided by the Southern California Seismic Network (SCSN) shows that our solutions generally provide better fit to the observed waveforms. Our algorithm may provide more robust CMT solutions for earthquakes in Southern California. In addition, the rapid and accurate full-wave CMT inversion has potential to extent to accurate near real-time ground-motion prediction based on 3D structure model for earthquake early warning purpose. When combined with real-time telemetered waveform recordings, our algorithm can provide (near) real-time ground-motion forecast.

  13. Mild recurrent neuropathy in CMT1B with a novel nonsense mutation in the extracellular domain of the MPZ gene

    PubMed Central

    Lagueny, A; Latour, P; Vital, A; Le Masson, G; Rouanet, M; Ferrer, X; Vital, C; Vandenberghe, A

    2001-01-01

    Clinical, electrophysiological, and neuropathological features are reported associated with a novel heterozygote point mutation in the extracellular domain of the MPZ gene, where a transversion at codon 71 in exon 3 leads to a codon stop: Glu71stop (ie GAA→TAA). A 36 year old woman developed a mild recurrent neuropathy after intensive manual work. The motor nerve conduction velocities were slow without conduction blocks and the nerve biopsy showed signs of demyelination-remyelination, axonal loss, and regular uncompacted myelin lamellae. She inherited the mutation from her father who displayed the same mutation with a normal phenotype. This nonsense mutation may cause a dosage difference of normal P0, and is probably underrepresented in the current mutation data bases. This report further extends the phenotype of MPZ mutations and also emphasises that mild phenotype of CMT1B may be more frequent than has been appreciated.

 PMID:11160475

  14. Growth hormone receptor (GHR) RNAi decreases proliferation and enhances apoptosis in CMT-U27 canine mammary carcinoma cell line.

    PubMed

    Pawłowski, K M; Popielarz, D; Szyszko, K; Gajewska, M; Motyl, T; Król, M

    2012-03-01

    Canine mammary gland has been identified as a major site of the extrapituitary growth hormone (GH) production. This finding is linked to its role in tumourigenesis of the mammary gland. Our previous studies indicated the role of GH and GH receptor (GHR) in regulation of proliferation and apoptosis. Thus, we have optimized the ghr RNA interference method in canine mammary carcinoma cell line CMT-U27. We have analysed the effect of GHR reduction on the intracellular signalling and the cell cycle and apoptosis. The results showed that GHR reduction decreased the p-ERK1/2 expression and caused increase of apoptosis and decrease in number of cells at S and G2M phases. This study indicates that GHR besides proliferative effect promotes growth by increasing cell survival. It can tilt the balance between proliferation and death in cancer cells. © 2011 Blackwell Publishing Ltd.

  15. CMT-linked loss-of-function mutations in GDAP1 impair store-operated Ca2+ entry-stimulated respiration

    PubMed Central

    González-Sánchez, Paloma; Pla-Martín, David; Martínez-Valero, Paula; Rueda, Carlos B.; Calpena, Eduardo; del Arco, Araceli; Palau, Francesc; Satrústegui, Jorgina

    2017-01-01

    GDAP1 is an outer mitochondrial membrane protein involved in Charcot-Marie-Tooth (CMT) disease. Lack of GDAP1 gives rise to altered mitochondrial networks and endoplasmic reticulum (ER)-mitochondrial interactions resulting in a decreased ER-Ca2+ levels along with a defect on store-operated calcium entry (SOCE) related to a misallocation of mitochondria to subplasmalemmal sites. The defect on SOCE is mimicked by MCU silencing or mitochondrial depolarization, which prevent mitochondrial calcium uptake. Ca2+ release from de ER and Ca2+ inflow through SOCE in neuroblastoma cells result in a Ca2+-dependent upregulation of respiration which is blunted in GDAP1 silenced cells. Reduced SOCE in cells with CMT recessive missense mutations in the α-loop of GDAP1, but not dominant mutations, was associated with smaller SOCE-stimulated respiration. These cases of GDAP1 deficiency also resulted in a decreased ER-Ca2+ levels which may have pathological implications. The results suggest that CMT neurons may be under energetic constraints upon stimulation by Ca2+ mobilization agonists and point to a potential role of perturbed mitochondria-ER interaction related to energy metabolism in forms of CMT caused by some of the recessive or null mutations of GDAP1. PMID:28220846

  16. [A case of Charcot-Marie-Tooth disease (CMT) type 1 complicated by diabetes mellitus (DM) showing bilateral phrenic nerve palsy].

    PubMed

    Takakura, Yuka; Furuya, Hirokazu; Yamashita, Ken-ichiro; Murai, Hiroyuki; Araki, Takehisa; Kikuchi, Hitoshi; Ohyagi, Yasumasa; Yamada, Takeshi; Kira, Jun-ichi

    2002-04-01

    We here report a 44-year-old woman with Charcot-Marie-Tooth disease (CMT) type 1 who showed severe bilateral phrenic nerve palsy (PNP). She had chronic progressive distal dominant muscle weakness and atrophy since early in her second decade and had been unable to walk by herself due to weakness of the legs since she was 40-years old. At that time, she was diagnosed with diabetes mellitus (DM). She also had difficulty breathing when she was in a supine position. On admission, sural nerve biopsy showed a marked decrease of large and small myelinated fibers and numerous onion bulb formations, which are compatible with CMT type 1. Chest X-ray showed bilateral elevation of the diaphragm, which was more marked on the right side, indicating bilateral PNP. Since it is reported that CMT patients show demyelination of the phrenic nerve subclinically, and DM itself may facilitate the development of PNP, periodic evaluations of respiratory function may thus be useful for preventing respiratory failure in patients with CMT, especially when it is complicated with DM.

  17. CMT-linked loss-of-function mutations in GDAP1 impair store-operated Ca(2+) entry-stimulated respiration.

    PubMed

    González-Sánchez, Paloma; Pla-Martín, David; Martínez-Valero, Paula; Rueda, Carlos B; Calpena, Eduardo; Del Arco, Araceli; Palau, Francesc; Satrústegui, Jorgina

    2017-02-21

    GDAP1 is an outer mitochondrial membrane protein involved in Charcot-Marie-Tooth (CMT) disease. Lack of GDAP1 gives rise to altered mitochondrial networks and endoplasmic reticulum (ER)-mitochondrial interactions resulting in a decreased ER-Ca(2+) levels along with a defect on store-operated calcium entry (SOCE) related to a misallocation of mitochondria to subplasmalemmal sites. The defect on SOCE is mimicked by MCU silencing or mitochondrial depolarization, which prevent mitochondrial calcium uptake. Ca(2+) release from de ER and Ca(2+) inflow through SOCE in neuroblastoma cells result in a Ca(2+)-dependent upregulation of respiration which is blunted in GDAP1 silenced cells. Reduced SOCE in cells with CMT recessive missense mutations in the α-loop of GDAP1, but not dominant mutations, was associated with smaller SOCE-stimulated respiration. These cases of GDAP1 deficiency also resulted in a decreased ER-Ca(2+) levels which may have pathological implications. The results suggest that CMT neurons may be under energetic constraints upon stimulation by Ca(2+) mobilization agonists and point to a potential role of perturbed mitochondria-ER interaction related to energy metabolism in forms of CMT caused by some of the recessive or null mutations of GDAP1.

  18. Diagnostic value of ultrastructural nerve examination in Charcot-Marie-Tooth disease: two CMT 1B cases with pseudo-recessive inheritance.

    PubMed

    Vallat, Jean-Michel; Magy, Laurent; Lagrange, Emmeline; Sturtz, Franck; Magdelaine, Corinne; Grid, Djamel; Tazir, Mériem

    2007-04-01

    We report two sporadic patients of CMT disease in different consanguineous families. The electrophysiological examination led to the diagnosis of a severe demyelinating neuropathy. The nerve biopsies exhibited numerous outfoldings of the myelin sheaths and onion-bulb proliferations. The consanguinity and the histological findings pointed to a diagnosis of CMT 4B. However, the detection of abnormal and regular widenings between the major dense lines of the myelin lamellae by electron microscopy led us to search for a P0 gene mutation. Two heterozygous mutations of this gene were identified: S63F and N131Y. Different aspects of uncompacted myelin lamellae have been described in some cases of P0 mutations and a few now appear to be quite specific to it. More than 30 genes are implicated in CMT and as mutation search is time- and money-consuming, we believe that in some selected patients ultrastructural examination of nerves, among other criteria, helps orientate the molecular diagnosis of CMT.

  19. Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability.

    PubMed

    Zhang, Feng; Seeman, Pavel; Liu, Pengfei; Weterman, Marian A J; Gonzaga-Jauregui, Claudia; Towne, Charles F; Batish, Sat Dev; De Vriendt, Els; De Jonghe, Peter; Rautenstrauss, Bernd; Krause, Klaus-Henning; Khajavi, Mehrdad; Posadka, Jan; Vandenberghe, Antoon; Palau, Francesc; Van Maldergem, Lionel; Baas, Frank; Timmerman, Vincent; Lupski, James R

    2010-06-11

    Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed that >99% of these rearrangements are recurrent and mediated by nonallelic homologous recombination (NAHR). Rare copy number variations (CNVs) generated by nonrecurrent rearrangements also exist in 17p12, but their underlying mechanisms are not well understood. We investigated 21 subjects with rare CNVs associated with CMT1A or HNPP by oligonucleotide-based comparative genomic hybridization microarrays and breakpoint sequence analyses, and we identified 17 unique CNVs, including two genomic deletions, ten genomic duplications, two complex rearrangements, and three small exonic deletions. Each of these CNVs includes either the entire PMP22 gene, or exon(s) only, or ultraconserved potential regulatory sequences upstream of PMP22, further supporting the contention that PMP22 is the critical gene mediating the neuropathy phenotypes associated with 17p12 rearrangements. Breakpoint sequence analysis reveals that, different from the predominant NAHR mechanism in recurrent rearrangement, various molecular mechanisms, including nonhomologous end joining, Alu-Alu-mediated recombination, and replication-based mechanisms (e.g., FoSTeS and/or MMBIR), can generate nonrecurrent 17p12 rearrangements associated with neuropathy. We document a multitude of ways in which gene function can be altered by CNVs. Given the characteristics, including small size, structural complexity, and location outside of coding regions, of selected rare CNVs, their identification remains a challenge for genome analysis. Rare CNVs may potentially represent an important portion of "missing heritability" for human diseases.

  20. The PpCMT chromomethylase affects cell growth and interacts with the homolog of LIKE HETEROCHROMATIN PROTEIN 1 in the moss Physcomitrella patens.

    PubMed

    Dangwal, Meenakshi; Kapoor, Sanjay; Kapoor, Meenu

    2014-02-01

    Chromomethylases (CMTs) are plant-specific cytosine DNA methyltransferases that are involved in maintenance of CpNpG methylation. In seed plants, histone methylation and interaction of CMT with LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) is essential for recruitment of CMT to target sites. LHP1 has been characterized as a putative component of the POLYCOMB REPRESSIVE COMPLEX1 (PRC1) in plants, and functions downstream of PRC2 to maintain genes in repressed state for orchestrated development. In the present study, we show that targeted disruption of PpCMT results in an approximately 50% reduction in global cytosine methylation levels. This affects growth of apical cells, predominantly growth of side branch initials emerging from chloronema cells. In some places, these cells develop thick walls with plasmolyzed cellular contents. Transcript accumulation patterns of genes involved in apical cell extension and metabolism of hemicelluloses, such as xyloglucans, in the primary cell walls decreased many fold in ppcmt mutant lines, as determined by real-time PCR. Using yeast two-hybrid method and bimolecular fluorescence complementation assay, we show that PpCMT and PpLHP1 interact through their chromo domains, while PpLHP1 homodimerizes through its chromo shadow domain. The results presented in this study provide insight into the role of the single chromomethylase, PpCMT, in proliferation of protonema filaments, and shed light on the evolutionary conservation of proteins interacting with these methylases in the early land plant, Physcomitrella patens. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  1. X-linked Charcot-Marie-Tooth (CMT) neuropathies (CMTX1, CMTX2, CMTX3) show different clinical phenotype and molecular genetics

    SciTech Connect

    Ionasescu, V.V.; Searby, C.C.; Ionasescu, R.

    1994-09-01

    The purpose of this study was to compare the X-linked dominant type CMTX1 (20 families) with X-linked recessive types CMTX2 and CMTX3 (2 families). The clinical phenotype was consistent with CMT peripheral neuropathy in all cases including distal weakness, atrophy and sensory loss, pes cavus and areflexia. Additional clinicial involvement of the central nervous system was present in one family with CMTX2 (mental retardation) and one family with CMTX3 (spastic paraparesis). Tight genetic linkage to Xq13.1 was present in 20 families with CMTX1 (Z=34.07 at {theta}=0) for the marker DXS453. Fifteen of the CMTX1 families showed point mutations of the connexin 32 coding region (5 nonsense mutations, 8 missense mutations, 2 deletions). Five CMTX1 neuropathy families showed no evidence of point mutations of the CX32 coding sequence. These findings suggest that the CMTX1 neuropathy genotype in these families may be the result of promoter mutations, 3{prime}-untranslated region mutations or exon/intron splice site mutations or a mutation with a different type of connexin but which has close structural similarities to CX32. No mutations of the CX32 coding region were found in the CMTX2 or CMTX3 families. Linkage to Xq13.1 was excluded in both families. Genetic linkage to Xp22.2 was present in the CMTX2 family (Z=3.54 at {theta}=0) for the markers DXS987 and DXS999. Suggestion of linkage to Xq26 (Z=1.81 at {theta}=0) for the marker DXS86 was present in the CMTX3 family.

  2. GJB1-associated X-linked Charcot-Marie-Tooth disease, a disorder affecting the central and peripheral nervous systems.

    PubMed

    Abrams, Charles K; Freidin, Mona

    2015-06-01

    Charcot-Marie-Tooth disease (CMT) is a group of inherited diseases characterized by exclusive or predominant involvement of the peripheral nervous system. Mutations in GJB1, the gene encoding Connexin 32 (Cx32), a gap-junction channel forming protein, cause the most common X-linked form of CMT, CMT1X. Cx32 is expressed in Schwann cells and oligodendrocytes, the myelinating glia of the peripheral and central nervous systems, respectively. Thus, patients with CMT1X have both central and peripheral nervous system manifestations. Study of the genetics of CMT1X and the phenotypes of patients with this disorder suggest that the peripheral manifestations of CMT1X are likely to be due to loss of function, while in the CNS gain of function may contribute. Mice with targeted ablation of Gjb1 develop a peripheral neuropathy similar to that seen in patients with CMT1X, supporting loss of function as a mechanism for the peripheral manifestations of this disorder. Possible roles for Cx32 include the establishment of a reflexive gap junction pathway in the peripheral and central nervous system and of a panglial syncitium in the central nervous system.

  3. A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: a dynamic histomorphometric and gene expression study.

    PubMed

    Ramamurthy, N; Bain, S; Liang, C T; Barnes, J; Llavaneras, A; Liu, Y; Puerner, D; Strachan, M J; Golub, L M

    2001-02-01

    Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis. In the current study, a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model. Forty-two, 6month old, female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehicle; c) OVX/1 mg/day CMT-8; d) OVX/2 mg/day CMT-8, e) OVX/1 mg/week Clodronate; and f) OVX/1 mg/day CMT-8 + 1 mg/week Clodronate, CMT-8 was administered by oral gavage, Clodronate injected S/C. Following sham surgery or OVX, the rats were treated for 90 days with CMT-8 or vehicle alone, injected at three different times with fluorochrome labels, the rats were sacrificed, and the tibiae excised for analysis by dynamic bone histomorphometry. Femurs were aseptically removed and analyzed for collagen, collagenase and osteopontin mRNAs by Northern and dot blot analysis. As expected, OVX decreased trabecular bone volume (BV/TV by 73.8% vs. sham p<.01), and also reduced trabecular thickness, numbers, and increased spacing. Bone loss in the OVX animals was partially prevented with either 2 mg/day CMT-8 or 1 mg/wk Clodronate (p<.01), while the 1 mg/day CMT-8 had no effect. Interestingly, the efficacy of the combination therapy of CMT-8 and Clodronate was significantly better than either treatment by itself, maintaining bone mass and structural indices at levels identical to sham values. OVX rats mRNA for collagen, collagenase and osteopontin were elevated indicating high-turnover bone loss. Only COMBO therapy significantly reduced the collagenase and osteopontin mRNA. In summary, CMT-8 mono-therapy (2 mg) alone partially inhibited bone loss in this animal model of osteoporosis. However, 1 mg/day (CMT-8) monotherapy had no effect on bone loss or bone mRNA levels and when combined with Clodronate, interacted to increase efficacy. Thus, a combination of a

  4. Botulinum toxin treatment of pes cavovarus in a child suffering from autosomal recessive axonal Charcot-Marie-Tooth neuropathy (AR-CMT2).

    PubMed

    Tiffreau, V; Allart, E; Dangleterre, C; Boutry, N; Petit, F; Cuisset, J M; Thevenon, A

    2015-06-01

    In a 12-year old girl suffering from autosomal recessive axonal Charcot-Marie-Tooth (CMT) neuropathy, pes cavovarus was treated with botulinum toxin injection in the tibialis posterior. The patient underwent a clinical evaluation, video analysis of spatiotemporal gait parameters and dynamic foot plantar pressure assessment before treatment and then two weeks, three months and six months thereafter. The video gait analysis revealed a decrease in varus during the swing phase of gait. The dynamic foot plantar pressure decreased by 50% in the excessive pressure at the side of the foot six months after the injection (maximal pressure=42.6N/cm2 before treatment and 18.9 N/cm2 after 6 month). Botulinum toxin injection appears to be an efficacious means of correcting pes cavovarus in CMT disease. A larger-scale clinical trial is now required to evaluate the putative longer-term preventive effect of this treatment on the pes cavus deformity.

  5. Isolation and expression analysis of genes encoding MET, CMT, and DRM methyltransferases in oil palm (Elaeis guineensis Jacq.) in relation to the 'mantled' somaclonal variation.

    PubMed

    Rival, Alain; Jaligot, Estelle; Beulé, Thierry; Finnegan, E Jean

    2008-01-01

    In oil palm (Elaeis guineensis Jacq.), approximately 5% of somatic embryo-derived regenerants show homeotic changes during floral development, involving an apparent feminization of male parts in flowers of both sexes, called the 'mantled' phenotype. This variant phenotype is associated with a reduction in the level of global DNA methylation. To explore possible relationships between DNA methylation level and accumulation of DNA-(cytosine-5) methyltransferase (DNMT) transcripts, the full-length coding sequences corresponding to three different DNMT families in oil palm, namely the MET, CMT, and DRM classes, have been isolated and characterized. The corresponding genes were designated as EgMET1, EgCMT1, and EgDRM1, and encode predicted polypeptides of 1543, 925, and 591 amino acid residues, respectively. Expression of oil palm DNMTs was compared between normal and variant calli and inflorescence tissues using quantitative reverse-transcription PCR. A consistent increase in transcript levels of EgMET1 and EgCMT1 was found in variant fast-growing calli relative to nodular-compact calli. Nodular-compact calli give rise to about 5% of abnormal regenerants whereas fast-growing calli generate 95% of 'mantled' palms in their clonal offspring and were previously demonstrated as having markedly hypomethylated DNA. In immature abnormal inflorescences only EgMET1 transcript levels were increased, while no changes in relative abundance of the EgCMT1 or EgDRM1 transcripts were observed. Therefore, the genome-wide hypomethylation previously described in 'mantled' material cannot be explained by a decrease in expression levels of the de novo or maintenance DNMTs, a paradox which has been previously reported in tumour cells, where there is evidence for global hypomethylation of DNA.

  6. Characterization of non-CG genomic hypomethylation associated with gamma-ray-induced suppression of CMT3 transcription in Arabidopsis thaliana.

    PubMed

    Kim, Ji Eun; Lee, Min Hee; Cho, Eun Ju; Kim, Ji Hong; Chung, Byung Yeoup; Kim, Jin-Hong

    2013-12-01

    Ionizing radiation causes various epigenetic changes, as well as a variety of DNA lesions such as strand breaks, cross-links, oxidative damages, etc., in genomes. However, radiation-induced epigenetic changes have rarely been substantiated in plant genomes. The current study investigates whether DNA methylation of Arabidopsis thaliana genome is altered by gamma rays. We found that genomic DNA methylation decreased in wild-type plants with increasing doses of gamma rays (5, 50 and 200 Gy). Irradiation with 200 Gy significantly increased the expression of transcriptionally inactive centromeric 180-bp (CEN) and transcriptionally silent information (TSI) repeats. This increase suggested that there was a substantial release of transcriptional gene silencing by gamma rays, probably by induction of DNA hypomethylation. High expression of the DNA demethylase ROS1 and low expression of the DNA methyltransferase CMT3 supported this hypothesis. Moreover, Southern blot analysis following digestion of genomic DNA with methylation-sensitive enzymes revealed that the DNA hypomethylation occured preferentially at CHG or CHH sites rather than CG sites, depending on the radiation dose. Unlike CEN and TSI repeats, the number of Ta3, AtSN1 and FWA repeats decreased in transcription but increased in non-CG methylation. In addition, the cmt3-11 mutant showed neither DNA hypomethylation nor transcriptional activation of silenced repeats upon gamma irradiation. Furthermore, profiles of genome-wide transcriptomes in response to gamma rays differed between the wild-type and cmt3-11 mutant. These results suggest that gamma irradiation induced DNA hypomethylation preferentially at non-CG sites of transcriptionally inactive repeats in a locus-specific manner, which depends on CMT3 activity.

  7. CMT-associated mutations in glycyl- and tyrosyl-tRNA synthetases exhibit similar pattern of toxicity and share common genetic modifiers in Drosophila.

    PubMed

    Ermanoska, Biljana; Motley, William W; Leitão-Gonçalves, Ricardo; Asselbergh, Bob; Lee, LaTasha H; De Rijk, Peter; Sleegers, Kristel; Ooms, Tinne; Godenschwege, Tanja A; Timmerman, Vincent; Fischbeck, Kenneth H; Jordanova, Albena

    2014-08-01

    Aminoacyl-tRNA synthetases are ubiquitously expressed proteins that charge tRNAs with their cognate amino acids. By ensuring the fidelity of protein synthesis, these enzymes are essential for the viability of every cell. Yet, mutations in six tRNA synthetases specifically affect the peripheral nerves and cause Charcot-Marie-Tooth (CMT) disease. The CMT-causing mutations in tyrosyl- and glycyl-tRNA synthetases (YARS and GARS, respectively) alter the activity of the proteins in a range of ways (some mutations do not impact charging function, while others abrogate it), making a loss of function in tRNA charging unlikely to be the cause of disease pathology. It is currently unknown which cellular mechanisms are triggered by the mutant enzymes and how this leads to neurodegeneration. Here, by expressing two pathogenic mutations (G240R, P234KY) in Drosophila, we generated a model for GARS-associated neuropathy. We observed compromised viability, and behavioral, electrophysiological and morphological impairment in flies expressing the cytoplasmic isoform of mutant GARS. Their features recapitulated several hallmarks of CMT pathophysiology and were similar to the phenotypes identified in our previously described Drosophila model of YARS-associated neuropathy. Furthermore, CG8316 and CG15599 - genes identified in a retinal degeneration screen to modify mutant YARS, also modified the mutant GARS phenotypes. Our study presents genetic evidence for common mutant-specific interactions between two CMT-associated aminoacyl-tRNA synthetases, lending support for a shared mechanism responsible for the synthetase-induced peripheral neuropathies. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Rapid full-wave centroid moment tensor (CMT) inversion in a three-dimensional earth structure model for earthquakes in Southern California

    NASA Astrophysics Data System (ADS)

    Lee, En-Jui; Chen, Po; Jordan, Thomas H.; Wang, Liqiang

    2011-07-01

    A central problem of seismology is the inversion of regional waveform data for models of earthquake sources. In regions such as Southern California, preliminary 3-D earth structure models are already available, and efficient numerical methods have been developed for 3-D anelastic wave-propagation simulations. We describe an automated procedure that utilizes these capabilities to derive centroid moment tensors (CMTs). The procedure relies on the use of receiver-side Green's tensors (RGTs), which comprise the spatial-temporal displacements produced by the three orthogonal unit impulsive point forces acting at the receivers. We have constructed a RGT database for 219 broad-band stations in Southern California using a tomographically improved version of the 3-D SCEC Community Velocity Model Version 4.0 (CVM4) and a staggered-grid finite-difference code. Finite-difference synthetic seismograms for any earthquake in our modelling volume can be simply calculated by extracting a small, source-centred volume from the RGT database and applying the reciprocity principle. The partial derivatives needed for the CMT inversion can be generated in the same way. We have developed an automated algorithm that combines a grid-search for suitable focal mechanisms and hypocentre locations with a Gauss-Newton optimization that further refines the grid-search results. Using this algorithm, we have determined CMT solutions for 165 small to medium-sized earthquakes in Southern California. Preliminary comparison with the CMT solutions provided by the Southern California Seismic Network (SCSN) shows that our solutions generally provide better fit to the observed waveforms. When applied to a large number of earthquakes, our algorithm may provide a more robust CMT catalogue for earthquakes in Southern California.

  9. Comparison of California Mastitis Test (CMT), Somatic Cell Counts (SCC) and bacteriological examinations for detection of camel (Camelus dromedarius) mastitis in Ethiopia.

    PubMed

    Abdel Gadir Atif, E; Hildebrandt, Goetz; Kleer, Josef N; Molla, Bayleyegn; Kyule, Moses N; Baumann, Maximilian P O

    2006-01-01

    A total of 956 quarter milk samples from 253 traditionally managed lactating camels were collected aseptically from Negele (Borena Region), Dire Dawa, and Gewane (Afar Region), Ethiopia, according to multi-stage sampling. The quarter milk samples were subjected to California Mastitis Test (CMT), Somatic Cell Counts (SCC) and bacteriological examinations. Five hundred and seventy one (59.7%) quarter milk samples had microorganisms. Of these, 428 (75.0%) had isolates that were identified as major pathogens (MAP) and 143 (25.0%) as minor pathogens (MIP). A positive correlation was found between CMT scores and bacteriological classes (MAP, MIP) (p-value = 0.00). Strong correlation (p-value = 0.00) between CMT scores and SCC was recorded. The differences among the median log SCC of bacteriological classes (MAP, MIP) were not significant (p-value = 0.24). Similarly, the application of the cut-off level of 2.5 x 10(5) ml(-1) indicated less agreement (p-value = 0.32) for bacteriological classes MAP and MIP.

  10. IGF-I and retinoic acid regulate the distribution pattern of IGFBPs synthesized by the canine mammary tumor cell line CMT-U335.

    PubMed

    Oosterlaken-Dijksterhuis, M A; Kwant, M M; Slob, A; Hellmén, E; Mol, J A

    1999-03-01

    Stromal-epithelial interactions modulate growth and development in normal and neoplastic mammary gland. The release of IGF binding proteins (IGFBPs) by the stromal compartment of the mammary gland may play a modulating role in the IGF-mediated proliferation of mammary epithelium. Therefore, the IGFBP-expression pattern of the canine mammary tumor cell line U335 (CMT-U335), which has a mesenchymal phenotype, was determined. In addition, the effects of IGFs and all trans retinoic acid (RA) on DNA synthesis, and IGFBP secretion and distribution were examined. The IGFBPs secreted by CMT-U335 were characterized as IGFBP-2, -4, -5, and -6. Moreover, CMT-U335 appeared to be a suitable mammary mesenchymal cell line for study of the regulatory factors of IGFBP expression and the mechanism(s) involved. IGFs and RA enhanced IGFBP concentrations in cell-conditioned medium with IGF-I and RA having an additive effect. The IGF-I-stimulated DNA synthesis, however, was inhibited by RA. The difference between IGF-I and RA was an enhanced IGFBP-5 binding to the extracellular matrix (ECM) by RA, whereas IGF-I reduced binding to the ECM. Because high doses of insulin had no significant effects on IGFBP concentrations in the medium, it is concluded that IGF-I-induced changes in IGFBP concentrations are not mediated by type-IIGF receptors and may be the consequence of IGFBP redistribution.

  11. A novel Gypsy founder mutation, p.Arg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes

    PubMed Central

    Gooding, R; Colomer, J; King, R; Angelicheva, D; Marns, L; Parman, Y; Chandler, D; Bertranpetit, J; Kalaydjieva, L

    2005-01-01

    Background: Linkage, haplotype and sequencing analysis in a large Spanish Gypsy kindred with multiple members affected by autosomal recessive peripheral neuropathy led to the identification of a novel mutation, p.Arg1109X, in the CMT4C gene. The screening of further unrelated patients, and of a panel of ethnically matched controls, showed that p.Arg1109X is an ancestral mutation which occurs in Gypsy populations across Europe and is the most common cause of autosomal recessive Charcot–Marie–Tooth disease in Spanish Gypsies. Objective: To report the identification of a novel Gypsy founder mutation causing autosomal recessive CMT4C disease in a sample of homozygous affected individuals. Results: The mutation was associated with a surprisingly broad spectrum of neuropathy phenotypes, with variation in the age at onset, rate of progression, severity of muscle and sensory involvement, the presence of scoliosis, and cranial nerve involvement. Conclusions: Ascertainment and further studies of CMT4C patients in this population will provide a unique opportunity for characterising the full range of clinical manifestations of the disease in a genetically homogeneous sample. PMID:16326826

  12. Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method.

    PubMed

    Slater, Howard; Bruno, Damien; Ren, Hua; La, Phung; Burgess, Trent; Hills, Louise; Nouri, Sara; Schouten, Jan; Choo, K H Andy

    2004-08-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5-Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5-Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation-dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost-effective technique suitable for fast, high-throughput testing and offers distinct advantages over other testing methods.

  13. A multicenter, randomized, double-blind, placebo-controlled trial of long-term ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL): the study protocol [EudraCT no.: 2006-000032-27].

    PubMed

    Pareyson, Davide; Schenone, Angelo; Fabrizi, Gian Maria; Santoro, Lucio; Padua, Luca; Quattrone, Aldo; Vita, Giuseppe; Gemignani, Franco; Visioli, Francesco; Solari, Alessandra

    2006-12-01

    There is no treatment for Charcot-Marie-Tooth disease 1A (CMT1A), but ascorbic acid (AA) is efficacious in the transgenic mouse model. Thus, a clinical trial of AA in CMT1A is warranted. The CMT-TRIAAL is a phase III randomized, double-blind, placebo-controlled study involving 222 CMT1A adults from eight Italian centers. Eligible for the study are symptomatic adults with genetically confirmed CMT1A. Treatment consists of 2-year oral AA (1500mg/day) or placebo. The primary trial endpoint is an improvement in CMT Neuropathy Score. Secondary efficacy endpoints are changes in distal arm and leg maximum voluntary isometric contraction; 10m timed walking; 9-hole-peg test; overall neuropathy limitations scale; pain and fatigue visual analog scales; health-related quality of life (SF-36); and electrophysiology. Clinical-electrophysiological assessments are performed at baseline and every 6 months thereafter. In consenting patients from three centers, skin biopsy is performed to evaluate PMP22 expression. The study will last 34 months, starting from March 2006.

  14. Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a Colombian family.

    PubMed

    Martin, Angela M; Maradei, Silvia J; Velasco, Harvy M

    2015-12-30

    Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A. The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.

  15. CMT for materials science

    SciTech Connect

    Kinney, J.

    1997-02-01

    This session is comprised of two articles by John Kinney describing biomedical and other uses for computerized tomography. In the first article, Kinney describes the use of a three-dimensional x-ray tomographic microscope to image the trabecular bone architecture of the proximal tibias of rats in vivo. Research in this field may help to detect the earliest stages of hypoestrogenemic bone loss and may help to more rapidly test the effectiveness of new clinical treatments for this major public health problem. The second article describes recent advances in X-ray tomography using synchrotron radiation to evaluate microstructures in ceramic matrix composites, bone loss in osteoporosis, and the development of carries lesions in teeth.

  16. Chemically modified tetracycline (CMT-8) and estrogen promote wound healing in ovariectomized rats: effects on matrix metalloproteinase-2, membrane type 1 matrix metalloproteinase, and laminin-5 gamma2-chain.

    PubMed

    Pirilä, Emma; Parikka, Mataleens; Ramamurthy, Nungavarm S; Maisi, Päivi; McClain, Steve; Kucine, Allan; Tervahartiala, Taina; Prikk, Kaiu; Golub, Lorne M; Salo, Tuula; Sorsa, Timo

    2002-01-01

    Estrogen deficiency is associated with impaired cutaneous wound healing. Remodeling of the extracellular matrix in wound healing involves the action of matrix metalloproteinases on basement membrane zone components, especially laminin-5. We studied the effects of estrogen and a potent matrix metalloproteinase inhibitor, chemically modified non-antimicrobial tetracycline, CMT-8, on wound healing in ovariectomized rats. At the tissue level, laminin-5 gamma2-chain expression was decreased and the migration-inductive 80 kDa form of laminin-5 gamma2-chain was absent in ovariectomized rats when compared with sham and CMT-8- or estrogen-treated ovariectomized animals as detected by Western blotting. The highest levels of gelatinolytic activity (matrix metalloproteinase-2 and -9) were found in sham animals. Levels were reduced in ovariectomized rats and were lowest after treating ovariectomized rats with CMT-8 or estrogen as analyzed by functional activity assay and zymography. The total amount of membrane type 1-matrix metalloproteinase was unchanged in all groups. We conclude that CMT-8 and estrogen can promote wound healing in ovariectomized rats, not only by normalizing wound bed total collagen content and structure, but also by recovering the expression and processing of key molecules in wound healing, i.e., laminin-5 gamma2-chain. This study shows, for the first time, the role of estrogen and CMT-8 in laminin-5 gamma2-chain modulation in vivo.

  17. A 1.5-Mb cosmid contig of the CMT1A duplication/HNPP deletion critical region in 17p11.2-p12

    SciTech Connect

    Murakami, Tatsufumi; Lupski, J.R.

    1996-05-15

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem duplication in chromosome 17p11.2-p12, and hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this locus. Both diseases appear to result from an altered copy number of the peripheral myelin protein-22 gene, PMP22, which maps within the critical region. To identify additional genes and characterize chromosomal elements, a 1.5-Mb cosmid contig of the CMT1A duplication/HNPP deletion critical region was assembled using a yeast artificial chromosome (YAC)-based isolation and binning strategy. Whole YAC probes were used for screening a high-density arrayed chromosome 17-specific cosmid library. Selected cosmids were spotted on dot blots and assigned to bins defined by YACs. This binning of cosmids facilitated the subsequent fingerprint analysis. The 1.5-Mb region was covered by 137 cosmids with a minimum overlap set of 52 cosmids assigned to 17 bins and 9 contigs. 20 refs., 2 figs.

  18. Melatonin and IL-25 modulate apoptosis and angiogenesis mediators in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumour cells.

    PubMed

    Gelaleti, G B; Borin, T F; Maschio-Signorini, L B; Moschetta, M G; Hellmén, E; Viloria-Petit, A M; Zuccari, D A P C

    2017-03-20

    Melatonin has oncostatic actions and IL-25 is active in inflammatory processes that induce apoptosis in tumor cells AIM: The aim of this study was to evaluate melatonin and IL-25 in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumor cells cultured as monolayers and tridimensional structures. The cells were treated with melatonin, IL-25 and IL-17B silencing gene and performed cell viability, gene and protein expression of caspase-3 and VEGFA (Vascular endothelial growth factor A) and an apoptosis membrane protein array. Treatment with 1 mM of melatonin reduced cell viability of both tumor cell lines, all treatments alone and combined significantly increased caspase-3 cleaved and proteins involved in the apoptotic pathway and reduced pro-angiogenic VEGFA, confirming the effectiveness of these potential promising treatments. This is the first study evaluating the potential use of these strategies in CF-41 and CMT-U229 cell lines and together encourages subsequent in vitro and in vivo studies for further exploration of clinical applications. © 2017 John Wiley & Sons Ltd.

  19. Comparative proteome analysis of three mouse lung adenocarcinoma CMT cell lines with different metastatic potential by two-dimensional gel electrophoresis and mass spectrometry.

    PubMed

    Zhang, Kelan; Wrzesinski, Krzysztof; Stephen, J Fey; Larsen, Peter Mose; Zhang, Xumin; Roepstorff, Peter

    2008-12-01

    Metastasis is a lethal attribute of a cancer and presents a continuing therapeutic challenge. Metastasis is a highly complex process and more knowledge about the mechanisms behind metastasis is highly desirable. Isogenic CMT cell lines were selected from a spontaneous mouse lung adenocarcinoma and characterized in vivo to have different metastatic potential. In this study, the comprehensive protein expression profiles of three of these CMT cell lines at passage 5, 15 and 35 were analyzed by 2-DE separation followed by MS identification. As a result, 82 and 40 unique proteins were found to be significantly up- or down-regulated between cell lines with different metastatic potential at passages 5 and 15, respectively. These proteins were identified by MS and most of them have previously been reported to be related to cancer development and/or metastasis. Bioinformatics analysis indicated that several of the proteins were involved in proteasome, cell-cycle and cell-communication pathways. Among them, some keratins, 14-3-3 proteins and 26S proteasome proteins were identified and their aberrant expression may be directly or indirectly involved in cancer development and metastasis. In conclusion, our comprehensive 2-DE-based proteomics studies revealed some candidate proteins, protein families and signaling pathways, which might be important in cancer development and metastasis.

  20. A 1.5-Mb cosmid contig of the CMT1A duplication/HNPP deletion critical region in 17p11.2-p12.

    PubMed

    Murakami, T; Lupski, J R

    1996-05-15

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1. 5-Mb tandem duplication in chromosome 17p11.2-p12, and hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this locus. Both diseases appear to result from an altered copy number of the peripheral myelin protein-22 gene, PMP22, which maps within the critical region. To identify additional genes and characterize chromosomal elements, a 1.5-Mb cosmid contig of the CMT1A duplication/HNPP deletion critical region was assembled using a yeast artificial chromosome (YAC)-based isolation and binning strategy. Whole YAC probes were used for screening a high-density arrayed chromosome 17-specific cosmid library. Selected cosmids were spotted on dot blots and assigned to bins defined by YACs. This binning of cosmids facilitated the subsequent fingerprint analysis. The 1.5-Mb region was covered by 137 cosmids with a minimum overlap set of 52 cosmids assigned to 17 bins and 9 contigs.

  1. Enigma of earthquakes at ridge-transform-fault plate boundaries - Distribution of non-double couple parameter of Harvard CMT solutions. [Centroid Moment Tensors

    SciTech Connect

    Kawakatsu, Hitoshi )

    1991-06-01

    The distribution of the non-double couple parameter of shallow earthquakes reported in the Harvard CMT catalogue shows systematic characteristics depending on the epicentral locations and types of fault mechanisms. The authors suggest that they can be explained by the presence of subevents with different double couple mechanisms in a single rupture sequence. The earthquakes at the ridge-transform-fault plate boundaries show a particularly interesting pattern. It is suggested that two types of faulting expected in the area (i.e., normal faults at ridges and strike slip faults at transform-faults) tend to occur almost simultaneously, although this hypothesis needs to be delineated by careful analyses using bodywave waveforms.

  2. Matrix and impurity element distributions in CdHgTe (CMT) and (Cd,Zn)(Te,Se) compounds by chemical analysis

    NASA Astrophysics Data System (ADS)

    Capper, P.; O'Keefe, E. S.; Maxey, C.; Dutton, D.; Mackett, P.; Butler, C.; Gale, I.

    1996-04-01

    This review describes several of the main techniques used to determine matrix element distributions and those which can provide a survey of impurity levels and assess deliberate doping concentrations in Cd xHg 1 - xTe and CdTe-based substrate materials. The most widely used method to non-destructively determine x is that of Fourier transform infrared (FTIR) spectrometry and lateral x variations in current bulk, LPE and MOVPE material measured by this technique will be presented. Auger electron spectrometry (AES) has been used on bevelled samples to assess variations in x with depth and interface widths in LPE, MOVPE and MBE layers and examples will be given. Near IR spectrometry is also now being used to monitor the variations in Zn and Se content, in CdZnTe and CdTeSe respectively, and results in this area will be described along with measurements of Zn on the micro-scale using AES. All of these techniques need to be calibrated against an absolute chemical analysis technique and we have used atomic absorption spectrometry (AAS). The latter technique also provides the accurate measure of dopant and impurity elements to standardise other techniques. Secondary ion mass spectrometry (SIMS) is mainly used for the determination of dopant depth distributions while laser scan mass spectrometry (LSMS) has the unique capability of providing a survey of low levels of impurities in thin epitaxial layers. Depth profiles of arsenic and iodine in MOVPE heterostructures, using SIMS, will be given. Impurity surveys, using LSMS, in bulk CMT and substrate materials and in CMT epitaxial layers grown by LPE, MOVPE and MBE will be described. Reported glow discharge mass spectrometry (GDMS) results on substrate materials will be compared to the present results.

  3. The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

    PubMed Central

    Inoue, Ken; Dewar, Ken; Katsanis, Nicholas; Reiter, Lawrence T.; Lander, Eric S.; Devon, Keri L.; Wyman, Dudley W.; Lupski, James R.; Birren, Bruce

    2001-01-01

    Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs) represent frequent genomic rearrangements resulting in two common inherited peripheral neuropathies, Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP). CMT1A and HNPP exemplify a paradigm for genomic disorders wherein unique genome architectural features result in susceptibility to DNA rearrangements that cause disease. A gene within the 1.4-Mb region, PMP22, is responsible for these disorders through a gene-dosage effect in the heterozygous duplication or deletion. However, the genomic structure of the 1.4-Mb region, including other genes contained within the rearranged genomic segment, remains essentially uncharacterized. To delineate genomic structural features, investigate higher-order genomic architecture, and identify genes in this region, we constructed PAC and BAC contigs and determined the complete nucleotide sequence. This CMT1A/HNPP genomic segment contains 1,421,129 bp of DNA. A low copy number repeat (LCR) was identified, with one copy inside and two copies outside of the 1.4-Mb region. Comparison between physical and genetic maps revealed a striking difference in recombination rates between the sexes with a lower recombination frequency in males (0.67 cM/Mb) versus females (5.5 cM/Mb). Hypothetically, this low recombination frequency in males may enable a chromosomal misalignment at proximal and distal CMT1A–REPs and promote unequal crossing over, which occurs 10 times more frequently in male meiosis. In addition to three previously described genes, five new genes (TEKT3, HS3ST3B1, NPD008/CGI-148, CDRT1, and CDRT15) and 13 predicted genes were identified. Most of these predicted genes are expressed only in embryonic stages. Analyses of the genomic region adjacent to proximal CMT1A–REP indicated an evolutionary mechanism for the formation of proximal CMT1A–REP and

  4. The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes.

    PubMed

    Inoue, K; Dewar, K; Katsanis, N; Reiter, L T; Lander, E S; Devon, K L; Wyman, D W; Lupski, J R; Birren, B

    2001-06-01

    Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A-REPs) represent frequent genomic rearrangements resulting in two common inherited peripheral neuropathies, Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP). CMT1A and HNPP exemplify a paradigm for genomic disorders wherein unique genome architectural features result in susceptibility to DNA rearrangements that cause disease. A gene within the 1.4-Mb region, PMP22, is responsible for these disorders through a gene-dosage effect in the heterozygous duplication or deletion. However, the genomic structure of the 1.4-Mb region, including other genes contained within the rearranged genomic segment, remains essentially uncharacterized. To delineate genomic structural features, investigate higher-order genomic architecture, and identify genes in this region, we constructed PAC and BAC contigs and determined the complete nucleotide sequence. This CMT1A/HNPP genomic segment contains 1,421,129 bp of DNA. A low copy number repeat (LCR) was identified, with one copy inside and two copies outside of the 1.4-Mb region. Comparison between physical and genetic maps revealed a striking difference in recombination rates between the sexes with a lower recombination frequency in males (0.67 cM/Mb) versus females (5.5 cM/Mb). Hypothetically, this low recombination frequency in males may enable a chromosomal misalignment at proximal and distal CMT1A-REPs and promote unequal crossing over, which occurs 10 times more frequently in male meiosis. In addition to three previously described genes, five new genes (TEKT3, HS3ST3B1, NPD008/CGI-148, CDRT1, and CDRT15) and 13 predicted genes were identified. Most of these predicted genes are expressed only in embryonic stages. Analyses of the genomic region adjacent to proximal CMT1A-REP indicated an evolutionary mechanism for the formation of proximal CMT1A-REP and the

  5. Homologous DNA exchanges in humans can be explained by the yeast double-strand break repair model: a study of 17p11.2 rearrangements associated with CMT1A and HNPP.

    PubMed

    Lopes, J; Tardieu, S; Silander, K; Blair, I; Vandenberghe, A; Palau, F; Ruberg, M; Brice, A; LeGuern, E

    1999-11-01

    Rearrangements in 17p11.2, responsible for the 1.5 Mb duplications and deletions associated, respectively, with autosomal dominant Charcot-Marie-Tooth type 1A disease (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are a suitable model for studying human recombination. Rearrangements in 17p11.2 are caused by unequal crossing-over between two homologous 24 kb sequences, the CMT1A-REPs, that flank the disease locus and occur in most cases within a 1.7 kb hotspot. We sequenced this hotspot in 28 de novo patients (25 CMT1A and three HNPP), in order to localize precisely, at the DNA sequence level, the crossing-overs. We show that some chimeric CMT1A-REPs in de novo patients (10/28) present conversion of DNA segments associated with the crossing-over. These rearrangements can be explained by the double-strand break (DSB) repair model described in yeast. Fine mapping of the de novo rearrangements provided evidence that the successive steps of this model, heteroduplex DNA formation, mismatch correction and gene conversion, occurred in patients. Furthermore, the model explains 17p11.2 recombinations between chromosome homologues as well as between sister chromatids. In addition, defective mismatch repair of the heteroduplex DNA, observed in two patients, resulted in two heterozygous chimeric CMT1A-REPs which can be explained, as in yeast, by post-meiotic segregation. This work supports the hypothesis that the DSB repair model of DNA exchange may apply universally from yeasts to humans.

  6. Optimizing and Evaluating an Integrated SPECT-CmT System Dedicated to Improved 3-D Breast Cancer Imaging

    DTIC Science & Technology

    2010-05-01

    are shown in Figure 2. The phantoms were positioned as close to the isocenter of the cone beam CT imaging system as possible (Figure 2), and scanned...the isocenter of the CmT system, enabling the system to tilt around the envelope of a hemi-sphere located at the isocenter , with radius equal to the... isocenter to detector distance of the new CmT system. The concept system design is shown in Figure 8 using accurately modeled computer aided design

  7. A High-Speed Target-Free Vision-Based Sensor for Bus Rapid Transit Viaduct Vibration Measurements Using CMT and ORB Algorithms

    PubMed Central

    Hu, Qijun; He, Songsheng; Wang, Shilong; Liu, Yugang; Zhang, Zutao; He, Leping; Wang, Fubin; Cai, Qijie; Shi, Rendan; Yang, Yuan

    2017-01-01

    Bus Rapid Transit (BRT) has become an increasing source of concern for public transportation of modern cities. Traditional contact sensing techniques during the process of health monitoring of BRT viaducts cannot overcome the deficiency that the normal free-flow of traffic would be blocked. Advances in computer vision technology provide a new line of thought for solving this problem. In this study, a high-speed target-free vision-based sensor is proposed to measure the vibration of structures without interrupting traffic. An improved keypoints matching algorithm based on consensus-based matching and tracking (CMT) object tracking algorithm is adopted and further developed together with oriented brief (ORB) keypoints detection algorithm for practicable and effective tracking of objects. Moreover, by synthesizing the existing scaling factor calculation methods, more rational approaches to reducing errors are implemented. The performance of the vision-based sensor is evaluated through a series of laboratory tests. Experimental tests with different target types, frequencies, amplitudes and motion patterns are conducted. The performance of the method is satisfactory, which indicates that the vision sensor can extract accurate structure vibration signals by tracking either artificial or natural targets. Field tests further demonstrate that the vision sensor is both practicable and reliable. PMID:28587275

  8. A High-Speed Target-Free Vision-Based Sensor for Bus Rapid Transit Viaduct Vibration Measurements Using CMT and ORB Algorithms.

    PubMed

    Hu, Qijun; He, Songsheng; Wang, Shilong; Liu, Yugang; Zhang, Zutao; He, Leping; Wang, Fubin; Cai, Qijie; Shi, Rendan; Yang, Yuan

    2017-06-06

    Bus Rapid Transit (BRT) has become an increasing source of concern for public transportation of modern cities. Traditional contact sensing techniques during the process of health monitoring of BRT viaducts cannot overcome the deficiency that the normal free-flow of traffic would be blocked. Advances in computer vision technology provide a new line of thought for solving this problem. In this study, a high-speed target-free vision-based sensor is proposed to measure the vibration of structures without interrupting traffic. An improved keypoints matching algorithm based on consensus-based matching and tracking (CMT) object tracking algorithm is adopted and further developed together with oriented brief (ORB) keypoints detection algorithm for practicable and effective tracking of objects. Moreover, by synthesizing the existing scaling factor calculation methods, more rational approaches to reducing errors are implemented. The performance of the vision-based sensor is evaluated through a series of laboratory tests. Experimental tests with different target types, frequencies, amplitudes and motion patterns are conducted. The performance of the method is satisfactory, which indicates that the vision sensor can extract accurate structure vibration signals by tracking either artificial or natural targets. Field tests further demonstrate that the vision sensor is both practicable and reliable.

  9. PMP22 exon 4 deletion causes ER retention of PMP22 and a gain-of-function allele in CMT1E.

    PubMed

    Wang, David S; Wu, Xingyao; Bai, Yunhong; Zaidman, Craig; Grider, Tiffany; Kamholz, John; Lupski, James R; Connolly, Anne M; Shy, Michael E

    2017-04-01

    To determine whether predicted fork stalling and template switching (FoSTeS) during mitosis deletes exon 4 in peripheral myelin protein 22 KD (PMP22) and causes gain-of-function mutation associated with peripheral neuropathy in a family with Charcot-Marie-Tooth disease type 1E. Two siblings previously reported to have genomic rearrangements predicted to involve exon 4 of PMP22 were evaluated clinically and by electrophysiology. Skin biopsies from the proband were studied by RT-PCR to determine the effects of the exon 4 rearrangements on exon 4 mRNA expression in myelinating Schwann cells. Transient transfection studies with wild-type and mutant PMP22 were performed in Cos7 and RT4 cells to determine the fate of the resultant mutant protein. Both affected siblings had a sensorimotor dysmyelinating neuropathy with severely slow nerve conduction velocities (<10 m/sec). RT-PCR studies of Schwann cell RNA from one of the siblings demonstrated a complete in-frame deletion of PMP22 exon 4 (PMP22Δ4). Transfection studies demonstrated that PMP22Δ4 protein is retained within the endoplasmic reticulum and not transported to the plasma membrane. Our results confirm that that FoSTeS-mediated genomic rearrangement produced a deletion of exon 4 of PMP22, resulting in expression of both PMP22 mRNA and protein lacking this sequence. In addition, we provide experimental evidence for endoplasmic reticulum retention of the mutant protein suggesting a gain-of-function mutational mechanism consistent with the observed CMT1E in this family. PMP22Δ4 is another example of a mutated myelin protein that is misfolded and contributes to the pathogenesis of the neuropathy.

  10. Near-regional CMT and multiple-point source solution of the September 5, 2012, Nicoya, Costa Rica Mw 7.6 (GCMT) earthquake

    NASA Astrophysics Data System (ADS)

    Quintero, Ronnie; Zahradník, Jiri; Sokos, Efthimios

    2014-11-01

    We use acceleration data from the Observatorio Vulcanologico y Sismologico, Universidad Nacional de Costa Rica (OVSICORI-UNA) and Laboratorio de Ingenieria Sismica, Universidad de Costa Rica (LIS-UCR) seismic network for the relocation and moment-tensor solution of the September 5, 2012, 14:42:03.35 UTC, Nicoya, Costa Rica earthquake (Mw 7.6 GCMT). Using different relocation methods we found a stable earthquake hypocenter, near the original OVSICORI-UNA location in the Nicoya Peninsula, NW Costa Rica at Lat 9.6943°N, Lon 85.5689°W, depth 15.3 km, associated with the subduction of the Cocos plate under Caribbean plate. Acceleration records at OVSICORI-UNA and LIS-UCR stations (94-171 km), at 0.03 < f < 0.06 Hz were used in the waveform inversion for a single-point centroid moment tensor (CMT). Using spatial grid search the centroid position was found at the depth of 30 km, situated at Lat 10.0559°N, Lon 85.4778°W, i.e. of about 41 km NNE from the epicenter. The centroid time is 14:42:18.89 UTC, i.e. 15.54 s later relative to the location-based origin time. The nodal plane (strike 318°, dip 27° and rake 115°) is the fault plane that agrees with the geometry of the subducted slab at Nicoya, NNW Costa Rica. Increasing the maximum studied frequency from 0.06 to 0.15 Hz, the multiple point source inversion model leads to two subevents. The first one was located near the centroid and the second subevent was situated 20 km along strike and 10 km down dip from the first subevent and 6 s later. The uncertainty of the source model was carefully examined using complementary inversion methods, viz the iterative deconvolution and non-negative least squares.

  11. CMT for soil science applications

    SciTech Connect

    Clausnitzer, V.; Hopmans, J.W.

    1997-02-01

    Today, x-ray computed microtomography provides us with the ability to noninvasively measure porous-media properties at a scale approaching 10 {mu}m. In contrast, traditional measurement techniques are either destructive or invasive, while still providing only limited information. Because the output from x-ray CT is directly related to density and atomic number, it is well suited for phase identification and concentration measurements.

  12. Effect of intramammary infusion of recombinant bovine GM-CSF and IL-8 on CMT score, somatic cell count, and milk mononuclear cell populations in Holstein cows with Staphylococcus aureus subclinical mastitis.

    PubMed

    Kiku, Yoshio; Ozawa, Tomomi; Takahashi, Hideyuki; Kushibiki, Shiro; Inumaru, Shigeki; Shingu, Hiroyuki; Nagasawa, Yuya; Watanabe, Atsushi; Hata, Eiji; Hayashi, Tomohito

    2017-03-09

    The effect of intramammary infusion of recombinant bovine granulocyte-macrophage colony-stimulating factor (rbGM-CSF) and interleukin-8 (rbIL-8) on mononuclear cell populations in quarters, somatic cell count (SCC) and the California Mastitis Test (CMT) score were investigated. From the selected cows with naturally occurring Staphylococcus aureus subclinical mastitis, one quarter of each cow were selected for the infusions of rbGM-CSF (400 μg/5 mL/quarter, n = 9), rbIL-8 (1 mg/5 mL/quarter, n = 9), and phosphate-buffered saline (5 mL/quarter, n = 7). The CMT score of both cytokines post infusion temporarily increased between days 0 and 1 and significantly decreased between days 7 and 14 compared to the preinfusion level. The SCC on day 14 after infusions of rbGM-CSF tended to be lower than that of the control group. The percentage of CD14+ cells increased on days 1 and 2 post infusion of rbGM-CSF. The percentage of CD4+ and CD8+ cells also increased on days 2 and 3, suggesting that the infusion of rbGM-CSF enhanced cellular immunity in the mammary gland. In contrast, the percentage of CD14+ cells decreased on days 0.25 and 1 post infusion of rbIL-8. No significant changes in the percentages of CD4+ and CD8+ cells in milk after infusion of rbIL-8 were evident during the experimental period, which suggested that rbIL-8 had little effect on the function of T cells in the mammary gland. These results indicated that rbGM-CSF and rbIL-8 decreased the CMT score by a different mechanism and may have a potential as therapeutic agents for subclinical mastitis.

  13. Progress in molecular diagnosis of Charcot-Marie-Tooth-disease type 1 (CMT 1, HMSN I) and hereditary neuropathy with liability to pressure palsies (HNPP) by fluorescence in situ hybridization (FISH)-detection of a potential genetic mosaicism

    SciTech Connect

    Bathke, K.; Liehr. T.; Ekici, A.

    1994-09-01

    We tested 20 CMT 1 patients characterized according to the criteria of the European CMT consortium by Southern hybridization of MspI restricted genomic DNA with probes pVAW409R1, pVAW412Hec and pEW401HE. In 11 of the 20 CMT 1 cases (55%), we observed a duplication in 17q11.2; one patient had a dinucleotide insertion in exon 6 of the PO-gene (5%). One HNPP case had a typical 17p11.2 deletion. Analysis of CA-repeats was performed with primers RM11GT and Mfd41; SSCP-analysis of the PO, PMP22 and Cx32-genes is in progress. FISH was carried out with probe pVAW409R1. 125 interphase nuclei were analyzed for each proband by counting the signals per nucleus. Normal cells show a characteristic distribution of signals: 1 signal in 5.9% of nuclei, 2 in 86.3% and 3 in 7.8%. A duplication is indicated by a shift to 3 signals in more than approximately 60% and 2 in less than 25% of the nuclei. In contrast, the 17p11.2 deletion of the HNPP patient shifts to 82.4% of nuclei with a single hybridization signal versus 14.4% with 2 signals. We detected one case with significantly abnormal distribution of interphase nuclei hybridization signals compared to cultures of normal cells and to those with 17p11.2 duplication or deletion: 3.2% nuclei revealed 1 signal, 48.0% two signals and 48.8% 3 signals, indicating a pathogenic but moderate dosis increase compared to the throughout duplicated cases. FISH with probe pVAW409R1 is a versatile tool to detect the HNPP deletion both in interphase nuclei and in metaphase chromosomes. In CMT 1 disease interphase nuclei are required for FISH analysis due to the small duplication of 1.5 Mbp. In contrast to Southern techniques, FISH is able to detect genetic mosaicism.

  14. The Evolutionary Chromosome Translocation 4;19 in Gorilla gorilla is Associated with Microduplication of the Chromosome Fragment Syntenic to Sequences Surrounding the Human Proximal CMT1A-REP

    PubMed Central

    Stankiewicz, Pawel; Park, Sung-Sup; Inoue, Ken; Lupski, James R.

    2001-01-01

    Many genomic disorders occur as a result of chromosome rearrangements involving low-copy repeats (LCRs). To better understand the molecular basis of chromosome rearrangements, including translocations, we have investigated the mechanism of evolutionary rearrangements. In contrast to several intrachromosomal rearrangements, only two evolutionary translocations have been identified by cytogenetic analyses of humans and greater apes. Human chromosome 2 arose as a result of a telomeric fusion between acrocentric chromosomes, whereas chromosomes 4 and 19 in Gorilla gorilla are the products of a reciprocal translocation between ancestral chromosomes, syntenic to human chromosomes 5 and 17, respectively. Fluorescence in situ hybridization (FISH) was used to characterize the breakpoints of the latter translocation at the molecular level. We identified three BAC clones that span translocation breakpoints. One breakpoint occurred in the region syntenic to human chromosome 5q13.3, between the HMG-CoA reductase gene (HMGCR) and RAS p21 protein activator 1 gene (RASA1). The second breakpoint was in a region syntenic to human chromosome 17p12 containing the 24 kb region-specific low-copy repeat-proximal CMT1A-REP. Moreover, we found that the t(4;19) is associated with a submicroscopic chromosome duplication involving a 19p chromosome fragment homologous to the human chromosome region surrounding the proximal CMT1A-REP. These observations further indicate that higher order genomic architecture involving low-copy repeats resulting from genomic duplication plays a significant role in karyotypic evolution. PMID:11435402

  15. Analysis of light propagation in slotted resonator based systems via coupled-mode theory.

    PubMed

    Hiremath, Kirankumar R; Niegemann, Jens; Busch, Kurt

    2011-04-25

    Optical devices with a slot configuration offer the distinct feature of strong electric field confinement in a low refractive index region and are, therefore, of considerable interest in many applications. In this work we investigate light propagation in a waveguide-resonator system where the resonators consist of slotted ring cavities. Owing to the presence of curved material interfaces and the vastly different length scales associated with the sub-wavelength sized slots and the waveguide-resonator coupling regions on the one hand, and the spatial extent of the ring on the other hand, this prototypical system provides significant challenges to both direct numerical solvers and semi-analytical approaches. We address these difficulties by modeling the slot resonators via a frequency-domain spatial Coupled-Mode Theory (CMT) approach, and compare its results with a Discontinuous Galerkin Time-Domain (DGTD) solver that is equipped with curvilinear finite elements. In particular, the CMT model is built on the underlying physical properties of the slotted resonators, and turns out to be quite efficient for analyzing the device characteristics. We also discuss the advantages and limitations of the CMT approach by comparing the results with the numerically exact solutions obtained by the DGTD solver. Besides providing considerable physical insight, the CMT model thus forms a convenient basis for the efficient analysis of more complex systems with slotted resonators such as entire arrays of waveguide-coupled resonators and systems with strongly nonlinear optical properties.

  16. Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves.

    PubMed

    Freidin, Mona; Asche-Godin, Samantha; Abrams, Charles K

    2015-01-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the human gene for Connexin32 (Cx32). This present study uses Ilumina Ref8-v2 BeadArray to examine the expression profiles of injured and uninjured sciatic nerves at 5, 7, and 14 days post-crush injury (dpi) from Wild Type (WT) and Cx32-knockout (Cx32KO) mice to identify the genes and signaling pathways that are dysregulated in the absence of Schwann cell Cx32. Given the assumption that loss of Schwann cell Cx32 disrupts the regeneration and maintenance of myelinated nerve leading to a demyelinating neuropathy in CMT1X, we initially hypothesized that nerve crush injury would result in significant increases in differential gene expression in Cx32KO mice relative to WT nerves. However, microarray analysis revealed a striking collapse in the number of differentially expressed genes at 5 and 7 dpi in Cx32KO nerves relative to WT, while uninjured and 14 dpi time points showed large numbers of differentially regulated genes. Further comparisons within each genotype showed limited changes in Cx32KO gene expression following crush injury when compared to uninjured Cx32KO nerves. By contrast, WT nerves exhibited robust changes in gene expression at 5 and 7 dpi with no significant differences in gene expression by 14dpi relative to uninjured WT nerve samples. Taken together, these data suggest that the gene expression profile in uninjured Cx32KO sciatic nerve strongly resembles that of a WT nerve following injury and that loss of Schwann cell Cx32 leads to a basal state of gene expression similar to that of an injured WT nerve. These findings support a role for Cx32 in non-myelinating and regenerating populations of Schwann cells in normal axonal maintenance in re-myelination, and regeneration of peripheral nerve following injury. Disruption of Schwann cell-axonal communication in CMT1X may cause dysregulation of signaling pathways that are essential for the

  17. Gene Expression Profiling Studies in Regenerating Nerves in a Mouse Model for CMT1X: Uninjured Cx32-Knockout Peripheral Nerves Display Expression Profile of Injured Wild Type Nerves

    PubMed Central

    Freidin, Mona; Asche-Godin, Samantha; Abrams, Charles K.

    2014-01-01

    X-linked Charcot–Marie–Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the human gene for Connexin32 (Cx32). This present study uses Ilumina Ref8-v2 BeadArray to examine the expression profiles of injured and uninjured sciatic nerves at 5, 7, and 14 days post-crush injury (dpi) from Wild Type (WT) and Cx32-knockout (Cx32KO) mice to identify the genes and signaling pathways that are dysregulated in the absence of Schwann cell Cx32. Given the assumption that loss of Schwann cell Cx32 disrupts the regeneration and maintenance of myelinated nerve leading to a demyelinating neuropathy in CMT1X, we initially hypothesized that nerve crush injury would result in significant increases in differential gene expression in Cx32KO mice relative to WT nerves. However, microarray analysis revealed a striking collapse in the number of differentially expressed genes at 5 and 7 dpi in Cx32KO nerves relative to WT, while uninjured and 14dpi time points showed large numbers of differentially regulated genes. Further comparisons within each genotype showed limited changes in Cx32KO gene expression following crush injury when compared to uninjured Cx32KO nerves. By contrast, WT nerves exhibited robust changes in gene expression at 5 and 7dpi with no significant differences in gene expression by 14dpi relative to uninjured WT nerve samples. Taken together, these data suggest the gene expression profile in uninjured Cx32KO sciatic nerve strongly resembles that of a WT nerve following injury and that loss of Schwann cell Cx32 leads to a basal state of gene expression similar to that of an injured WT nerve. These findings support a role for Cx32 in non-myelinating and regenerating populations of Schwann cells in normal axonal maintenance in re-myelination, and regeneration of peripheral nerve following injury. Disruption of Schwann cell-axonal communication in CMT1X may cause dysregulation of signaling pathways that are essential for the

  18. Near-field tsunami forecast system based on near real-time seismic moment tensor estimation in the regions of Indonesia, the Philippines, and Chile

    NASA Astrophysics Data System (ADS)

    Inazu, Daisuke; Pulido, Nelson; Fukuyama, Eiichi; Saito, Tatsuhiko; Senda, Jouji; Kumagai, Hiroyuki

    2016-05-01

    We have developed a near-field tsunami forecast system based on an automatic centroid moment tensor (CMT) estimation using regional broadband seismic observation networks in the regions of Indonesia, the Philippines, and Chile. The automatic procedure of the CMT estimation has been implemented to estimate tsunamigenic earthquakes. A tsunami propagation simulation model is used for the forecast and hindcast. A rectangular fault model based on the estimated CMT is employed to represent the initial condition of tsunami height. The forecast system considers uncertainties due to two possible fault planes and two possible scaling laws and thus shows four possible scenarios with these associated uncertainties for each estimated CMT. The system requires approximately 15 min to estimate the CMT after the occurrence of an earthquake and approximately another 15 min to make the tsunami forecast results including the maximum tsunami height and its arrival time at the epicentral region and near-field coasts available. The retrospectively forecasted tsunamis were evaluated by the deep-sea pressure and tide gauge observations, for the past eight tsunamis ( M w 7.5-8.6) that occurred throughout the regional seismic networks. The forecasts ranged from half to double the amplitudes of the deep-sea pressure observations and ranged mostly within the same order of magnitude as the maximum heights of the tide gauge observations. It was found that the forecast uncertainties increased for greater earthquakes (e.g., M w > 8) because the tsunami source was no longer approximated as a point source for such earthquakes. The forecast results for the coasts nearest to the epicenter should be carefully used because the coasts often experience the highest tsunamis with the shortest arrival time (e.g., <30 min).

  19. Conformational changes associated with L16P and T118M mutations in the membrane-embedded PMP22 protein, consequential in CMT-1A.

    PubMed

    Bello, Martiniano; Torres, Mixtli J; Méndez-Tenorio, Alfonso; Correa-Basurto, José

    2017-10-01

    Peripheral myelin protein 22 (PMP22) resides in the plasma membrane and is required for myelin formation in the peripheral nervous system. Excess PMP22 mutants accumulate in the endoplasmic reticulum (ER) resulting in the inherited neuropathies of Charcot-Marie-Tooth disease. However, there was no evidence of the structure of PMP22 or how mutations affect its folding. Therefore, in this study, we combined bioinformatics and homology modeling approaches to obtain three-dimensional native and mutated PMP22 models and its anchoring to a POPC membrane, submitted to .5-μs MD simulations, to determine how the L16P and T118M mutations affect the conformational behavior of PMP22. In addition, we investigated the ability of the native and mutated species to accumulate in the ER, via interaction with RER1, by combining protein-protein docking and MD simulations, taking the conformations that were most representative of the native and mutated PMP22 systems and RER1 conformations. Principal component analysis over MD simulations revealed that L16P and T118M mutations resulted in increased structural instability compared to the native form, which is consistent with previous experimental findings of increased structural fluctuations along a loop connecting transmembrane α-helix1 and α-helix2. Docking and MD simulations coupled with the MMGBSA approach allowed the identification that the binding interface for the PMP22-RER1 complex takes place through transmembrane α-helix1 and α-helix2, with higher effective binding free energy values between the mutated PMP22 systems and RER1 than for the native PMP22, mainly through van der Waals interactions.

  20. Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular ischemia: a randomized controlled trial.

    PubMed

    Sharifipour, Farideh; Razzaghi, Mohammadreza; Ramezani, Alireza; Azarmina, Mohsen; Yaseri, Mehdi; Soheilian, Roham; Soheilian, Masoud

    2016-04-01

    The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect.

  1. Evaluation of earthquake parameters used in the Indonesian Tsunami Early Warning System

    NASA Astrophysics Data System (ADS)

    Madlazim; Prastowo, Tjipto

    2016-02-01

    Twenty-two of a total of 30 earthquake events reported by the Indonesian Agency for Geophysics, Climatology and Meteorology during the time period 2007-2010 were falsely issued as tsunamigenic by the Indonesian Tsunami Early Warning System (Ina-TEWS). These 30 earthquakes were of different magnitudes and occurred in different locations. This study aimed to evaluate the performance of the Ina-TEWS using common earthquake parameters, including the earthquake magnitude, origin time, depth, and epicenter. In total, 298 datasets assessed by the Ina-TEWS and the global centroid moment tensor (CMT) method were assessed. The global CMT method is considered by almost all seismologists to be a reference for the determination of these parameters as they have been proved to be accurate. It was found that the earthquake magnitude, origin time, and depth provided by the Ina-TEWS were significantly different from those given in the global CMT catalog, whereas the latitude and longitude positions of the events provided by both tsunami assessment systems were coincident. The performance of the Ina-TEWS, particularly in terms of accuracy, remains questionable and needs to be improved.

  2. CMT for transport in porous media

    SciTech Connect

    Schwartz, L.

    1997-02-01

    This session is comprised of an outline of uses for x-ray microtomography in the field of petroleum geology. Calculations, diagrams, and color photomicrographs depict the many applications of synchrotron x-ray microtomograpy in determining transport properties and fluid flow characteristics of reservoir rocks, micro-porosity in carbonates, and aspects of multi-phase transport.

  3. The evolution of ANL CMT gloveboxes

    SciTech Connect

    Malecha, R. F.; Frigo, A. A.; Preuss, D. E.

    2000-07-06

    This report summarizes the following topics: the design approach based upon user-friendly concepts; utilization of existing component designs; cost effectiveness; schedule; and adaptable to project process changes without losing overall effectiveness of user-friendly approach.

  4. Gap junctions in inherited human disorders of the central nervous system

    PubMed Central

    Scherer, Steven S.

    2011-01-01

    CNS glia and neurons express connexins, the proteins that form gap junctions in vertebrates. We review the connexins expressed by oligodendrocytes and astrocytes, and discuss their proposed physiologic roles. Of the 21 members of the human connexin family, mutations in three are associated with significant central nervous system manifestations. For each, we review the phenotype and discuss possible mechanisms of disease. Mutations in GJB1, the gene for connexin 32 (Cx32) cause the second most common form of Charcot-Marie-Tooth disease (CMT1X). Though the only consistent phenotype in CMT1X patients is a peripheral demyelinating neuropathy, CNS signs and symptoms have been found in some patients with CMT1X. Recessive mutations in GJC2, the gene for Cx47, are one cause of Pelizaeus-Merzbacher-like disease (PMLD), which is characterized by nystagmus within the first 6 months of life, cerebellar ataxia by 4 years, and spasticity by 6 years of age. MRI imaging shows abnormal myelination. A different recessive GJC2 mutation causes a form of hereditary spastic paraparesis, which is a milder phenotype than PMLD. Dominant mutations in GJA1, the gene for Cx43, cause oculodentodigital dysplasia (ODDD), a pleitropic disorder characterized by oculo-facial abnormalities including micropthalmia, microcornia and hypoplastic nares, syndactyly of the fourth to fifth fingers and dental abnormalities. Neurologic manifestations, including spasticity and gait difficulties, are often but not universally seen. Recessive GJA1 mutations cause Hallermann-Streiff syndrome, a disorder showing substantial overlap with ODDD. PMID:21871435

  5. Four novel connexin 32 mutations in X-linked Charcot-Marie-Tooth disease. Phenotypic variability and central nervous system involvement.

    PubMed

    Karadima, Georgia; Koutsis, Georgios; Raftopoulou, Maria; Floroskufi, Paraskewi; Karletidi, Karolina-Maria; Panas, Marios

    2014-06-15

    Charcot-Marie-Tooth (CMT) disease, the most common hereditary neuropathy, is clinically and genetically heterogeneous. X-linked CMT (CMTX) is usually caused by mutations in the gap junction protein b 1 gene (GJB1) coding for connexin 32 (Cx32). The clinical manifestations of CMTX are characterized by significant variability, with some patients exhibiting central nervous system (CNS) involvement. We report four novel mutations in GJB1, c.191G>A (p.Cys64Tyr), c.508G>T (p.Val170Phe), c.778A>G (p.Lys260Glu) and c.300C>G (p.His100Gln) identified in four unrelated Greek families. These mutations were characterized by variable phenotypic expression, including a family with the Roussy-Lévy syndrome, and three of them were associated with mild clinical CNS manifestations. Copyright © 2014. Published by Elsevier B.V.

  6. Microbial Enhanced Oil Recovery in Fractional-Wet Systems: A Pore-Scale Investigation

    SciTech Connect

    Armstrong, Ryan T.; Wildenschild, Dorthe

    2012-10-24

    Microbial enhanced oil recovery (MEOR) is a technology that could potentially increase the tertiary recovery of oil from mature oil formations. However, the efficacy of this technology in fractional-wet systems is unknown, and the mechanisms involved in oil mobilization therefore need further investigation. Our MEOR strategy consists of the injection of ex situ produced metabolic byproducts produced by Bacillus mojavensis JF-2 (which lower interfacial tension (IFT) via biosurfactant production) into fractional-wet cores containing residual oil. Two different MEOR flooding solutions were tested; one solution contained both microbes and metabolic byproducts while the other contained only the metabolic byproducts. The columns were imaged with X-ray computed microtomography (CMT) after water flooding, and after MEOR, which allowed for the evaluation of the pore-scale processes taking place during MEOR. Results indicate that the larger residual oil blobs and residual oil held under relatively low capillary pressures were the main fractions recovered during MEOR. Residual oil saturation, interfacial curvatures, and oil blob sizes were measured from the CMT images and used to develop a conceptual model for MEOR in fractional-wet systems. Overall, results indicate that MEOR was effective at recovering oil from fractional-wet systems with reported additional oil recovered (AOR) values between 44 and 80%; the highest AOR values were observed in the most oil-wet system.

  7. Subclinical mastitis in dairy cows in Swiss organic and conventional production systems.

    PubMed

    Roesch, Markus; G Doherr, Marcus; Schären, Walter; Schällibaum, Melchior; Blum, Jürg W

    2007-02-01

    The objective was to compare the prevalence of subclinical mastitis (SM) and of udder pathogens in 60 Swiss organic (OP) and 60 conventional production systems (CP). Cows (n=970) were studied for SM prevalence and udder pathogens at median 31 d and 102 d post partum. Cows showing a >or=1+ positive California Mastitis Test (CMT) in at least one quarter were considered to have SM. Cow-level prevalences of SM for visits at 31 d and 102 d post partum (39% and 40% in OP and 34% and 35% in CP) were similar, but quarter-level prevalences of SM were higher (P<0.02) in OP than CP (15% and 18% in OP and 12% and 15% in CP). Median somatic cell counts in milk at 31 d post partum were higher (P<0.05) in OP than CP cows (43000 and 28000 cells/ml, respectively), but were similar at 102 d post partum in OP and CP cows (45000 and 38000 cells/ml, respectively). In milk samples from quarters showing a CMT reaction >or=2+ the prevalences of coagulase negative staphylococci were lower (P<0.05) at 102 d post partum, whereas prevalences of non-agalactiae streptococci were higher (P<0.05) in OP than in CP cows at 31 d and 102 d post partum. In conclusion, under Swiss conditions, subclinical mastitis is a greater problem in organic than in conventional production systems, but differences are not marked.

  8. High resolution x-ray CMT: Reconstruction methods

    SciTech Connect

    Brown, J.K.

    1997-02-01

    This paper qualitatively discusses the primary characteristics of methods for reconstructing tomographic images from a set of projections. These reconstruction methods can be categorized as either {open_quotes}analytic{close_quotes} or {open_quotes}iterative{close_quotes} techniques. Analytic algorithms are derived from the formal inversion of equations describing the imaging process, while iterative algorithms incorporate a model of the imaging process and provide a mechanism to iteratively improve image estimates. Analytic reconstruction algorithms are typically computationally more efficient than iterative methods; however, analytic algorithms are available for a relatively limited set of imaging geometries and situations. Thus, the framework of iterative reconstruction methods is better suited for high accuracy, tomographic reconstruction codes.

  9. Revisiting the thermodynamic relations in AdS /CMT models

    NASA Astrophysics Data System (ADS)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2017-03-01

    Motivated by the recent unified approach to the Smarr-like relation of anti-de Sitter (AdS) planar black holes in conjunction with the quasilocal formalism on conserved charges, we revisit the quantum statistical and thermodynamic relations of hairy AdS planar black holes. By extending the previous results, we identify the hairy contribution in the bulk and show that the holographic computation can be improved so that it is consistent with the bulk computation. We argue that the first law can be retained in its universal form and that the relation between the on-shell renormalized Euclidean action and its free energy interpretation in gravity may also be undeformed even with the hairy contribution in hairy AdS black holes.

  10. Characterization of the Novel CMT Enzyme TEM-154.

    PubMed

    Robin, Frédéric; Delmas, Julien; Machado, Elisabete; Bouchon, Bernadette; Peixe, Luísa; Bonnet, Richard

    2011-03-01

    TEM-154, identified in Portugal in 2004, associated the substitutions observed in the extended-spectrum β-lactamase (ESBL) TEM-12 and in the inhibitor-resistant penicillinase (IRT) TEM-33. This enzyme exhibited hydrolytic activity against ceftazidime and a low level of resistance to clavulanic acid. Surprisingly, the substitution Met69Leu enhanced the catalytic efficiency of oxyimino β-lactams conferred by the substitution Arg164Ser. Its discovery confirms the dissemination of the complex mutant group of TEM enzymes in European countries.

  11. Novel and tightly regulated resorcinol and cumate-inducible expression systems for Streptomyces and other actinobacteria.

    PubMed

    Horbal, Liliya; Fedorenko, Victor; Luzhetskyy, Andriy

    2014-10-01

    Inducible expression is a versatile genetic tool for controlling gene transcription, determining gene functions and other uses. Herein, we describe our attempts to create several inducible systems based on a cumate or a resorcinol switch, a hammerhead ribozyme, the LacI repressor, and isopropyl β-d-thiogalactopyranoside (IPTG). We successfully developed a new cumate (p-isopropylbenzoic acid)-inducible gene switch in actinobacteria that is based on the CymR regulator, the operator sequence (cmt) from the Pseudomonas putida cumate degradation operon and P21 synthetic promoter. Resorcinol-inducible expression system is also functional and is composed of the RolR regulator and the PA3 promoter fused with the operator (rolO) from the Corynebacterium glutamicum resorcinol catabolic operon. Using the gusA (β-glucuronidase) gene as a reporter, we showed that the newly generated expression systems are tightly regulated and hyper-inducible. The activity of the uninduced promoters is negligible in both cases. Whereas the induction factor reaches 45 for Streptomyces albus in the case of cumate switch and 33 in the case of resorcinol toggle. The systems are also dose-dependent, which allows the modulation of gene expression even from a single promoter. In addition, the cumate system is versatile, given that it is functional in different actinomycetes. Finally, these systems are nontoxic and inexpensive, as these are characteristics of cumate and resorcinol, and they are easy to use because inducers are water-soluble and easily penetrate cells. Therefore, the P21-cmt-CymR and PA3-rolO-RolR systems are powerful tools for engineering actinobacteria.

  12. Microtubule dynamics in the peripheral nervous system: A matter of balance.

    PubMed

    Almeida-Souza, Leonardo; Timmerman, Vincent; Janssens, Sophie

    2011-11-01

    The special architecture of neurons in the peripheral nervous system, with axons extending for long distances, represents a major challenge for the intracellular transport system. Two recent studies show that mutations in the small heat shock protein HSPB1, which cause an axonal type of Charcot-Marie-Tooth (CMT) neuropathy, affect microtubule dynamics and impede axonal transport. Intriguingly, while at presymptomatic age the neurons in the mutant HSPB1 mouse show a hyperstable microtubule network, at postsymptomatic age, the microtubule network completely lost its stability as reflected by a marked decrease in tubulin acetylation levels. We here propose a model explaining the role of microtubule stabilization and tubulin acetylation in the pathogenesis of HSPB1 mutations.

  13. Oscillations of relative inclination angles in compact extrasolar planetary systems

    NASA Astrophysics Data System (ADS)

    Becker, Juliette C.; Adams, Fred C.

    2016-01-01

    The Kepler mission has detected dozens of compact planetary systems with more than four transiting planets. This sample provides a collection of close-packed planetary systems with relatively little spread in the inclination angles of the inferred orbits. A large fraction of the observational sample contains limited multiplicity, begging the question whether there is a true diversity of multitransiting systems, or if some systems merely possess high mutual inclinations, allowing them to appear as single-transiting systems in a transit-based survey. This paper begins an exploration of the effectiveness of dynamical mechanisms in exciting orbital inclination within exoplanetary systems of this class. For these tightly packed systems, we determine that the orbital inclination angles are not spread out appreciably through self-excitation. In contrast, the two Kepler multiplanet systems with additional non-transiting planets are susceptible to oscillations of their inclination angles, which means their currently observed configurations could be due to planet-planet interactions alone. We also provide constraints and predictions for the expected transit duration variations for each planet. In these multiplanet compact Kepler systems, oscillations of their inclination angles are remarkably hard to excite; as a result, they tend to remain continually mutually transiting (CMT-stable). We study this issue further by augmenting the planet masses and determining the enhancement factor required for oscillations to move the systems out of transit. The oscillations of inclination found here inform the recently suggested dichotomy in the sample of Solar systems observed by Kepler.

  14. Tunable triple Fano resonances based on multimode interference in coupled plasmonic resonator system.

    PubMed

    Li, Shilei; Zhang, Yunyun; Song, Xiaokang; Wang, Yilin; Yu, Li

    2016-07-11

    In this paper, an asymmetric plasmonic structure composed of two MIM (metal-insulator-metal) waveguides and two rectangular cavities is reported, which can support triple Fano resonances originating from three different mechanisms. And the multimode interference coupled mode theory (MICMT) including coupling phases is proposed based on single mode coupled mode theory (CMT), which is used for describing and explaining the multiple Fano resonance phenomenon in coupled plasmonic resonator systems. Just because the triple Fano resonances originate from three different mechanisms, each Fano resonance can be tuned independently or semi-independently by changing the parameters of the two rectangular cavities. Such, a narrow 'M' type of double Lorentzian-like line-shape transmission windows with the position and the full width at half maximum (FWHM) can be tuned freely is constructed by changing the parameters of the two cavities appropriately, which can find widely applications in sensors, nonlinear and slow-light devices.

  15. Stuck in traffic: an emerging theme in diseases of the nervous system.

    PubMed

    Neefjes, Jacques; van der Kant, Rik

    2014-02-01

    The past decade has seen an explosion of DNA sequencing activities and many mutations and genetic variances underlying neurological and neurodegenerative diseases have been determined. This wealth of genetic data is now placed in molecular pathways revealing the nodes that underlie the disrupted processes. Many mutations in neurological diseases affect proteins controlling endosomal/lysosomal transport. Although the age of onset of these diseases range from juvenile [i.e., Niemann-Pick type C (NPC) and Charcot-Marie-Tooth (CMT) disease] to late onset (Parkinson's and Alzheimer's disease), deregulation of endosomal transport is a common theme. This review summarizes how elucidating the genetic basis for the various neurological diseases has advanced our understanding of the endo-lysosomal system and why the various mutations all translate into similar disease phenotypes.

  16. Feedback from educational supervisors and trainees on the implementation of curricula and the assessment system for core medical training.

    PubMed

    Johnson, Gavin; Barrett, James; Jones, Mike; Parry, David; Wade, Winnie

    2008-10-01

    A pilot of core medical training (CMT) was conducted in 2006-7 with 160 trainees and 130 supervisors in the 10 hospitals within the Mersey Deanery. Questionnaires and focus groups were used to gain feedback from trainees and supervisors in relation to the components of CMT (the curricula, workplace-based assessments, appraisal, and the e-portfolio). There was generally a positive attitude to the CMT package. In particular the opportunities to give and receive feedback were appreciated; the e-portfolio was identified as helpful for recording assessment outcomes and supporting educational development for the trainees. The workplace-based assessments were well received. Many of the benefits of the components of CMT depended on the skill of the supervisor. The time required for effective training supervision and workplace-based assessments was identified as an important issue. This pilot was invaluable in informing the widespread implementation of CMT in 2007.

  17. Cochlear implantation in a patient with deafness induced by Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathies).

    PubMed

    Postelmans, J T F; Stokroos, R J

    2006-06-01

    Charcot-Marie-Tooth disease (CMT), also named hereditary motor and sensory neuropathies (HMSN), comprises a clinically and genetically heterogeneous group of disorders affecting the peripheral nervous system. Deafness induced by CMT is clinically distinct among the genetically heterogeneous group of CMT disorders. Deafness in CMT patients is associated with point mutations or deletions in the transmembrane domain in the peripheral myelin gene (PMP) 22, which are in close proximity to the extracellular component of this gene. We present a patient with deafness induced by CMT type 1A, undergoing cochlear implantation. Prior investigations showed good results due to replacing a synchronous impulse by means of cochlear implantation in patients with auditory neuropathy.

  18. system

    NASA Astrophysics Data System (ADS)

    Garcilazo, H.; Valcarce, A.; Vijande, J.

    2017-07-01

    Using local central Yukawa-type Malfliet-Tjon interactions reproducing the low-energy parameters and phase shifts of the nn system, and the latest updates of the nΛ and ΛΛ Nijmegen ESC08c potentials, we study the possible existence of a bound state. Our results indicate that the is unbound, being just above threshold. We discuss the role played by the 1 S 0 nn repulsive term of the Yukawa-type Malfliet-Tjon interaction. Supported by COFAA-IPN (México), Ministerio de Economía, Industria y Competitividad and EU FEDER (FPA2013-47443, FPA2015-69714-REDT, FPA2016-77177), Junta de Castilla y León (SA041U16) and Generalitat Valenciana PrometeoII/2014/066

  19. Noradrenergic transmission in the central medial thalamic nucleus modulates the electroencephalographic activity and emergence from propofol anesthesia in rats.

    PubMed

    Fu, Bao; Yu, Tian; Yuan, Jie; Gong, Xingrui; Zhang, Mazhong

    2017-03-01

    At present, the mechanisms by which general anesthetics causing loss of consciousness remain unclear. The central medial thalamic nucleus (CMT) is a rarely studied component of the midline thalamic complex, which is deemed to be a part of the nonspecific arousal system. Although the CMT participates in modulating arousal and receives excitatory noradrenergic projections from locus coeruleus, it remains unknown whether the noradrenergic pathway in the CMT takes part in modulating the arousal system. Therefore, we hypothesized that noradrenergic transmission in the CMT is involved in modulating induction and emergence of propofol anesthesia. First, we infused norepinephrine (NE) into the CMT to observe the role of CMT noradrenergic pathway in modulating the anesthetic state induced by propofol. The results showed that microinjection of NE into the CMT accelerated emergence from propofol anesthesia, but had no impact on the induction of or sensitivity to propofol anesthesia in rats. In addition, infusion of NE into the CMT caused electroencephalography changes in the prefrontal cortex and the anterior cingulate cortex. Finally, we used a whole-cell patch clamp to examine the effects of NE on neuronal excitability and GABAergic transmission in the CMT. In the CMT slices, propofol suppressed neuronal excitability and enhanced GABAergic transmission, while application of NE partly reversed these effects. These findings support the hypothesis that the CMT noradrenergic pathway plays an important role in modulating the emergence from general anesthesia. © 2017 International Society for Neurochemistry.

  20. Multicloud parametrization of mesoscale convective systems for the ITCZ

    NASA Astrophysics Data System (ADS)

    Khouider, B.; Moncrieff, M. W.

    2014-12-01

    Mesoscale convective systems (MCS), aligned approximately parallel to the background low-level wind shear, are ubiquitous in the Eastern Pacific intertropical convergence zone (ITCZ). They are believed to control the local Hadley circulation and have a nontrivial momentum feedback on the ambient shear. They also play a central role in the two-way interactions between convection and the synoptic and planetary scale waves. They do so by serving as both the building block for organized convection, which involves congestus cloud decks that moisten and precondition the environment for deep convection which in turn is lagged by stratiform anvils, and as a conveyer belt for convective momentum transport (CMT). Here, we propose an extension of the multicloud model of Khouider and Majda (2006) to make the stratiform anvils more sensitive to the background wind shear profile. We do so by invoking two layers of moisture in the free troposphere instead of one, in addition to the boundary layer. Linear stability, in a wind shear background consisting of both mid-level and low-level easterly jets, representing, simultaneously, the Tropical Easterly and African Easterly jets, features the usual synoptic scale instability of the multicloud model plus two new instability bands at the meso-alpha and meso-beta scales, respectively. The meso-alpha and meso-beta modes constitute a paradigm for the dynamics of shear parallel convective systems with the meso-alpha waves being the quasi-stationary systems. In this talk we will present limited domain 3D simulations, without rotation, of realistic shear parallel lines of convection with parallel stratifrom anvils moving eastward, with a steering level in the upper troposphere, as a mesoscale envelope of the individual convective cells moving inwards, with a steering level in the lower troposphere. This provides, among other things, an excellent example of nontrivial CMT effect on the background low-level wind. It results in a narrow channel

  1. Analysis of wall heat capacity effects on core makup tank drain-down behavior in ROSA/AP600 experiments

    SciTech Connect

    Kondo, Masaya; Yonomoto, Taisuke; Asaka, Hideaki

    1997-12-01

    The thermal-hydraulic behavior of the core makeup tank (CMT) during scaled integral experiments on the Westinghouse AP600 reactor design was analyzed using the RELAP5/Mod3 (version 5M5) code. The natural circulation rate through the CMT was predicted well, although the prediction of the thermal stratification in the CMT had a problem due to inability to predict multidimensional mixing in the CMT upper regions. The over-scaled CMT metal mass in the experimental facility affected the CMT drain-down behavior in two experiments: (i) a multiple-failure experiment where the system depressurization became extremely slow due to the simulated failure of the ADS valves; and (ii) a relatively-large break experiment where the CMT started draining before thermal stratification developed in the CMT water inventory. In both experiments, the CMT wall became a heat sink and was a large steam condensation site. This had a effect to limit the CMT drain rate. 6 refs., 15 figs.

  2. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis.

    PubMed

    Chen, Huan-Xiong; Tang, Sheng-Ping; Gao, Fu-Tang; Xu, Jiang-Long; Jiang, Xian-Ping; Cao, Juan; Fu, Gui-Bing; Sun, Ke; Liu, Shi-Zhe; Shi, Wei

    2014-11-01

    In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the

  3. Prevalence and Predictors of Breastfeeding After Childhood Abuse.

    PubMed

    Eagen-Torkko, Meghan; Low, Lisa Kane; Zielinski, Ruth; Seng, Julia S

    To describe the prevalence and predictors of breastfeeding intent and outcomes in women with histories of childhood maltreatment trauma (CMT), including those with posttraumatic stress disorder (PTSD). Secondary analysis of a prospective observational cohort study of the effects of PTSD on perinatal outcomes. Prenatal clinics in three health systems in the Midwestern United States. Women older than 18 years expecting their first infants, comprising three groups: women who experienced CMT but did not have PTSD (CMT-resilient), women with a history of CMT and PTSD (CMT-PTSD), and women with no history of CMT (CMT-nonexposed). Secondary analysis of an existing data set in which first-time mothers were well-characterized on trauma history, PTSD, depression, feeding plans, feeding outcomes, and several other factors relevant to odds of breastfeeding success. Intent to breastfeed was similar among the three groups. Women in the CMT-resilient group were twice as likely to breastfeed exclusively at 6 weeks (60.5%) as women in the CMT-PTSD group (31.1%). Compared with women in the CMT-nonexposed group, women in the CMT-resilient group were more likely to exclusively breastfeed. Four factors were associated with increased likelihood of any breastfeeding at 6 weeks: prenatal intent to breastfeed, childbirth education, partnered, and a history of CMT. Four factors were associated with decreased odds of breastfeeding: African American race, PTSD, major depression, and low level of education (high school or less). Posttraumatic stress disorder is more important than childhood maltreatment trauma history in determining likelihood of breastfeeding success. Further research on the promotion of breastfeeding among PTSD-affected women who have experienced CMT is indicated. Copyright © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  4. Application of coupled mode theory on radiative heat transfer between layered Lorentz materials

    NASA Astrophysics Data System (ADS)

    Lin, Chungwei; Wang, Bingnan; Teo, Koon Hoo

    2017-05-01

    The coupled mode theory (CMT) provides a simple and clear framework to analyze the radiation energy exchange between reservoirs. We apply CMT to analyze the radiative heat transfer between layered Lorentz materials whose dielectric functions can be approximated by the Lorentz oscillator model. By comparing the transmissivity computed by the exact solution to that computed by CMT, we find that CMT generally gives a good approximation for this class of materials. The biggest advantage of CMT analysis, in our opinion, is that only the (complex) resonant energies are needed to obtain the radiation energy transfer; the knowledge of the spatial profile of resonances is not required. Several issues, including how to choose the resonant modes, what these modes represent, and the limitation of this method, are discussed. Finally, we also apply the CMT method to the electronic systems, demonstrating the generality of this formalism.

  5. Real time earthquake information and tsunami estimation system for Indonesia, Philippines and Central-South American regions

    NASA Astrophysics Data System (ADS)

    Pulido Hernandez, N. E.; Inazu, D.; Saito, T.; Senda, J.; Fukuyama, E.; Kumagai, H.

    2015-12-01

    Southeast Asia as well as Central-South American regions are within the most active seismic regions in the world. To contribute to the understanding of source process of earthquakes the National Research Institute for Earth Science and Disaster Prevention NIED maintains the international seismic Network (ISN) since 2007. Continuous seismic waveforms from 294 broadband seismic stations in Indonesia, Philippines, and Central-South America regions are received in real time at NIED, and used for automatic location of seismic events. Using these data we perform automatic and manual estimation of moment tensor of seismic events (Mw>4.5) by using the SWIFT program developed at NIED. We simulate the propagation of local tsunamis in these regions using a tsunami simulation code and visualization system developed at NIED, combined with CMT parameters estimated by SWIFT. The goals of the system are to provide a rapid and reliable earthquake and tsunami information in particular for large seismic, and produce an appropriate database of earthquake source parameters and tsunami simulations for research. The system uses the hypocenter location and magnitude of earthquakes automatically determined at NIED by the SeisComP3 system (GFZ) from the continuous seismic waveforms in the region, to perform the automated calculation of moment tensors by SWIFT, and then carry out the automatic simulation and visualization of tsunami. The system generates maps of maximum tsunami heights within the target regions and along the coasts and display them with the fault model parameters used for tsunami simulations. Tsunami calculations are performed for all events with available automatic SWIFT/CMT solutions. Tsunami calculations are re-computed using SWIFT manual solutions for events with Mw>5.5 and centroid depths shallower than 100 km. Revised maximum tsunami heights as well as animation of tsunami propagation are also calculated and displayed for the two double couple solutions by SWIFT

  6. End-to-End Concurrent Multipath Transfer Using Transport Layer Multihoming

    DTIC Science & Technology

    2006-07-01

    5.3). 5.1 Implementation Details BSD-SCTP (with CMT) is freely available as part of the KAME project [2]. While BSD- SCTP works with all BSD systems...experimentation with, CMT. 106 BIBLIOGRAPHY [1] Future combat systems website. http://www.globalsecurity.org/military/systems/ground/fcs.htm. [2] KAME Project

  7. Neuropathology of some hereditary conditions affecting central and peripheral nervous system.

    PubMed

    Martin, J J; Ceuterick, C

    2002-03-01

    Neuropathology plays a crucial role in the phenotypic individualization of hereditary disorders affecting the central and peripheral nervous system even if molecular genetics represents the most essential step in describing the genotypes. The neuropathological description of phenotypes and genotypes can be used for refining clinical skills and understanding many clinical, neurophysiological and neuroradiological features. It contributes to the diagnosis of such disorders. The use of immunohistochemical techniques in combination with molecular genetics improves also our knowledge of their pathogenesis and might participate to the future development of therapeutic strategies. We discuss new features of spino-cerebellar ataxia (SCA) type 7 and of a recently identified SCA17 in order to illustrate the significance of the neuronal intranuclear inclusions (NIIs) described in various CAG/polyglutamine repeat expansion diseases. In the field of the peripheral neuropathies we present data on a newly described autosomal recessive Charcot-Marie-Tooth disease (CMT4F) with mutations in the periaxin gene. We document a dysjunction between myelin loops and axolemma with disappearance of the septate-like junctions or transverse bands. The significance of this dysjunction is not yet elucidated. We hope to show by these examples that the combination of classical and new neuropathological methods is useful in the study of hereditary disorders of the nervous system.

  8. The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy

    PubMed Central

    Pehlivan, Davut; Beck, Christine R.; Okamoto, Yuji; Harel, Tamar; Akdemir, Zeynep H.C.; Jhangiani, Shalini N.; Withers, Marjorie A.; Goksungur, Meryem Tuba; Carvalho, Claudia M.B.; Czesnik, Dirk; Gonzaga-Jauregui, Claudia; Wiszniewski, Wojciech; Muzny, Donna M.; Gibbs, Richard A.; Rautenstrauss, Bernd; Sereda, Michael W.; Lupski, James R.

    2017-01-01

    Purpose Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of genetic disorders of the peripheral nervous system. Copy-number variants (CNVs) contribute significantly to CMT, as duplication of PMP22 underlies the majority of CMT1 cases. We hypothesized that CNVs and/or single-nucleotide variants (SNVs) might exist in patients with CMT with an unknown molecular genetic etiology. Methods Two hundred patients with CMT, negative for both SNV mutations in several CMT genes and for CNVs involving PMP22, were screened for CNVs by high-resolution oligonucleotide array comparative genomic hybridization. Whole-exome sequencing was conducted on individuals with rare, potentially pathogenic CNVs. Results Putatively causative CNVs were identified in five subjects (~2.5%); four of the five map to known neuropathy genes. Breakpoint sequencing revealed Alu-Alu-mediated junctions as a predominant contributor. Exome sequencing identified MFN2 SNVs in two of the individuals. Conclusion Neuropathy-associated CNV outside of the PMP22 locus is rare in CMT. Nevertheless, there is potential clinical utility in testing for CNVs and exome sequencing in CMT cases negative for the CMT1A duplication. These findings suggest that complex phenotypes including neuropathy can potentially be caused by a combination of SNVs and CNVs affecting more than one disease-associated locus and contributing to a mutational burden. PMID:26378787

  9. High-performance IR thermography system based on Class II Thermal Imaging Common Modules

    NASA Astrophysics Data System (ADS)

    Bell, Ian G.

    1991-03-01

    The Class II Thermal Imaging Common Modules were originally developed for the U.K. Ministry of Defence as the basis of a number of high performance thermal imaging systems for use by the British Armed Forces. These systems are characterized by high spatial resolution, high thermal resolution and real time thermal image update rate. A TICM II thermal imaging system uses a cryogenically cooled eight element Cadmium- Mercury-Telluride (CMT) SPRITE (Signal PRocessing In The Element) detector which is mechanically scanned over the thermal scene to be viewed. The TALYTHERM system is based on a modified TICM II thermal image connected to an IBM PC-AT compatible computer having image processing hardware installed and running the T.E.M.P.S. (Thermal Emission Measurement and Processing System) software package for image processing and data analysis. The operation of a TICM II thermal imager is briefly described highlighting the use of the SPRITE detector which coupled with a serial/parallel scanning technique yields high temporal, spatial and thermal resolutions. The conversion of this military thermal image into thermography system is described, including a discussion of the modifications required to a standard imager. The technique for extracting temperature information from a real time thermal image and how this is implemented in a TALYTHERM system is described. The D.A.R.T. (Discrete Attenuation of Radiance Thermography) system which is based on an extensively modified TICM II thermal imager is also described. This system is capable of measuring temperatures up to 1000 degrees C whilst maintaining the temporal and spatial resolutions inherent in a TICM II imager. Finally applications of the TALYTHERM in areas such as NDT (Non Destructive Testing), medical research and military research are briefly described.

  10. Microstructure and Properties of Lap Joint Between Aluminum Alloy and Galvanized Steel by CMT

    NASA Astrophysics Data System (ADS)

    Niu, Song; Chen, Su; Dong, Honggang; Zhao, Dongsheng; Zhang, Xiaosheng; Guo, Xin; Wang, Guoqiang

    2016-05-01

    Lap joining of 1-mm-thick Novelist AC 170 PX aluminum alloy to 1.2-mm-thick ST06 Z galvanized steel sheets for automotive applications was conducted by cold metal transfer advanced welding process with ER4043 and ER4047 filler wires. Under the optimized welding parameters with ER4043 filler wire, the tensile shear strength of joint was 189 MPa, reaching 89% of the aluminum alloy base metal. Microstructure and elemental distribution were characterized by optical metalloscope and electron probe microanalysis. The lap joints with ER4043 filler wire had smaller wetting angle and longer bonded line length with better wettability than with ER4047 filler wire during welding with same parameters. The needle-like Al-Fe-Si intermetallic compounds (IMCs) were spalled into the weld and brought negative effect to the tensile strength of joints. With increasing welding current, the needle-like IMCs grew longer and spread further into the weld, which would deteriorate the tensile shear strength.

  11. Boundary-Layer Transition on Large-Scale CMT Graphite Nosetips at Reentry Conditions

    DTIC Science & Technology

    1981-01-01

    a carbon arc (or tungsten ) reference source are recorded on identical film and are processed simultaneously with the model photograph, and (3...configuration is a reverse-taper plug that is swaged in place in the model forebody. Larger nosetips, which were required for expanding the range of...using either a carbon-arc light source or a tungsten source, depending on the desired calibration range--were simultaneously developed. These

  12. Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene.

    PubMed

    James, P A; Cader, M Z; Muntoni, F; Childs, A-M; Crow, Y J; Talbot, K

    2006-11-14

    We screened 100 patients with inherited and sporadic lower motor neuron degeneration and identified three novel missense mutations in the glycyl-tRNA synthetase (GARS) gene. One mutation was in the anticodon binding domain and associated with onset in early childhood and predominant involvement of the lower limbs, thus extending the phenotype associated with GARS mutations.

  13. Cadmium mercury telluride infrared detectors

    NASA Astrophysics Data System (ADS)

    Elliott, C. T.

    Signal Processing In The Element (SPITE) detectors used in high performance thermal imaging systems are discussed. Developments to improve spatial and temperature resolution are outlined. Focal plane arrays of electronically scanned two-dimensional arrays of CMT detectors are treated. Use of photovoltaic CMT detectors hybridized with silicon addressing circuits is reported. Research to raise the operating temperature of infrared detectors is summarized.

  14. Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal root ganglia - a possible explanation for peripheral nervous system involvement in Charcot-Marie-Tooth 2A.

    PubMed

    Kawalec, Maria; Zabłocka, Barbara; Kabzińska, Dagmara; Neska, Jacek; Beręsewicz, Małgorzata

    2014-01-01

    Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential for mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mutations in the mitofusin 2 gene cause axonal Charcot-Marie-Tooth type 2A (CMT2A), an inherited disease affecting peripheral nerve axons. The precise mechanism by which mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is a hypothesis suggesting the involvement of reduced expression of a homologous protein, mitofusin 1 (Mfn1), in the peripheral nervous system, and less effective compensation of defective mitofusin 2 by mitofusin 1. We therefore aimed to perform an analysis of the mitofusin 1 and mitofusin 2 mRNA and protein expression profiles in different mouse tissues, with special attention paid to dorsal root ganglia (DRGs), as parts of the peripheral nervous system. Quantitative measurement relating to mRNA revealed that expression of the Mfn2 gene dominates over Mfn1 mainly in mouse DRG, as opposed to other nervous system samples and other tissues studied. This result was further supported by Western blot evaluation. Both these sets of data confirm the hypothesis that the cellular consequences of mutations in the mitofusin 2 gene can mostly be manifested in the peripheral nervous system.

  15. Next-Generation Systemic Acquired Resistance1[W][OA

    PubMed Central

    Luna, Estrella; Bruce, Toby J.A.; Roberts, Michael R.; Flors, Victor; Ton, Jurriaan

    2012-01-01

    Systemic acquired resistance (SAR) is a plant immune response to pathogen attack. Recent evidence suggests that plant immunity involves regulation by chromatin remodeling and DNA methylation. We investigated whether SAR can be inherited epigenetically following disease pressure by Pseudomonas syringae pv tomato DC3000 (PstDC3000). Compared to progeny from control-treated Arabidopsis (Arabidopsis thaliana; C1), progeny from PstDC3000-inoculated Arabidopsis (P1) were primed to activate salicylic acid (SA)-inducible defense genes and were more resistant to the (hemi)biotrophic pathogens Hyaloperonospora arabidopsidis and PstDC3000. This transgenerational SAR was sustained over one stress-free generation, indicating an epigenetic basis of the phenomenon. Furthermore, P1 progeny displayed reduced responsiveness of jasmonic acid (JA)-inducible genes and enhanced susceptibility to the necrotrophic fungus Alternaria brassicicola. This shift in SA- and JA-dependent gene responsiveness was not associated with changes in corresponding hormone levels. Instead, chromatin immunoprecipitation analyses revealed that SA-inducible promoters of PATHOGENESIS-RELATED GENE1, WRKY6, and WRKY53 in P1 plants are enriched with acetylated histone H3 at lysine 9, a chromatin mark associated with a permissive state of transcription. Conversely, the JA-inducible promoter of PLANT DEFENSIN1.2 showed increased H3 triple methylation at lysine 27, a mark related to repressed gene transcription. P1 progeny from the defense regulatory mutant non expressor of PR1 (npr1)-1 failed to develop transgenerational defense phenotypes, demonstrating a critical role for NPR1 in expression of transgenerational SAR. Furthermore, the drm1drm2cmt3 mutant that is affected in non-CpG DNA methylation mimicked the transgenerational SAR phenotype. Since PstDC3000 induces DNA hypomethylation in Arabidopsis, our results suggest that transgenerational SAR is transmitted by hypomethylated genes that direct priming of SA

  16. GNSS Enhancements of the Tsunami Warning System at the National Tsunami Warning Center

    NASA Astrophysics Data System (ADS)

    Johnson, P. A.; Nyland, D. L.; Varnado, C.; Whitmore, P.; MacPherson, K.; Ohlendorf, S. J.; Huang, P.

    2016-12-01

    The National Tsunami Warning Center (NTWC) is working as part of a joint NOAA-NASA project to incorporate into its workflow Global Navigation Satellite System (GNSS) data. The basis of the system is to use GPS and GPS-with-accelerometer data to determine earthquake-induced near-source ground displacements to rapidly determine the earthquake magnitude and fault displacement in order to more quickly and accurately forecast tsunami wave heights. Partners include Jet Propulsion Laboratory (JPL), Scripps Institute of Oceanography, Central Washington University (CWU), the University of Washington, UC Berkeley, and our sister center, the Pacific Tsunami Warning Center (PTWC). We are currently in Phase 1 of 3. Here, the NTWC and our partners are defining roles and responsibilities, defining hardware and software requirements, migrating software, and identifying basic data requirements: selecting a prototype network, including number and configuration of stations. We are migrating existing software to an operational Earthworm system which supports the ingest of several real-time GPS data sets; computes magnitudes from displacement; estimates static offset; performs a fault slip inversion; and computes a FastCMT (line source). Successes so far include the establishment of data connections and ingest of real-time GNSS and seismogeodetic data, and the implementation of MwPD, MwPGD, and static offset algorithms. The ultimate goal of Phase 1 is the integration of these modules and others developed by our partners into the operational tsunami warning system at the Tsunami Warning Centers. By January 2017, we anticipate being done with Phase 1. This presentation will give an update of the project and will show the system as it stands at the NTWC. Included will be examples of the data flowing into the NTWC, schematic diagrams of data flow and algorithm implementation, optimization procedures, and preliminary results.

  17. Expert System Management System

    DTIC Science & Technology

    1991-08-30

    Expert System Management System (ESMS) Small Business Innovative Research Contract developed a distributed fault-tolerant expert system shell for...multiple expert systems in a multiprocessor environment. The ESMS contained four domain specific expert systems called Manager Expert System , Route...Planner Expert System , Weapon Expert System , and Situation Awareness and Display Expert System . The ESMS expert system shell was written in LISP

  18. Mutation of SIMPLE in Charcot–Marie–Tooth 1C alters production of exosomes

    PubMed Central

    Zhu, Hong; Guariglia, Sara; Yu, Raymond Y. L.; Li, Wenjing; Brancho, Deborah; Peinado, Hector; Lyden, David; Salzer, James; Bennett, Craig; Chow, Chi-Wing

    2013-01-01

    Charcot–Marie–Tooth (CMT) disease is an inherited neurological disorder. Mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE) account for the rare autosomal-dominant demyelination in CMT1C patients. Understanding the molecular basis of CMT1C pathogenesis is impeded, in part, by perplexity about the role of SIMPLE, which is expressed in multiple cell types. Here we show that SIMPLE resides within the intraluminal vesicles of multivesicular bodies (MVBs) and inside exosomes, which are nanovesicles secreted extracellularly. Targeting of SIMPLE to exosomes is modulated by positive and negative regulatory motifs. We also find that expression of SIMPLE increases the number of exosomes and secretion of exosome proteins. We engineer a point mutation on the SIMPLE allele and generate a physiological mouse model that expresses CMT1C-mutated SIMPLE at the endogenous level. We find that CMT1C mouse primary embryonic fibroblasts show decreased number of exosomes and reduced secretion of exosome proteins, in part due to improper formation of MVBs. CMT1C patient B cells and CMT1C mouse primary Schwann cells show similar defects. Together the data indicate that SIMPLE regulates the production of exosomes by modulating the formation of MVBs. Dysregulated endosomal trafficking and changes in the landscape of exosome-mediated intercellular communications may place an overwhelming burden on the nervous system and account for CMT1C molecular pathogenesis. PMID:23576546

  19. Therapeutic options in Charcot-Marie-Tooth diseases.

    PubMed

    Mathis, Stéphane; Magy, Laurent; Vallat, Jean-Michel

    2015-04-01

    Charcot-Marie-Tooth (CMT) diseases represent a heterogeneous genetic disorder (more than 80 genes are implicated in these inherited neuropathies), but sharing a similar phenotype. In recent years, advances in molecular genetics and molecular biology, and also the development of various animal models of CMT, have led to a better understanding. Taken together, this knowledge represents a prerequisite for the development of future therapies in CMT, and in peripheral nervous system disorders in general. The efficacy of various substances has been shown in vitro and also in vivo (in animal models); but, no significant positive effect has yet been confirmed in humans. However, some of these trials are still in development, and we may expect positive results in the future. Although CMT is still an incurable disease, symptomatic treatments (physiotherapy, surgery, analgesic, etc.) are crucial to improve the quality of life of CMT patients.

  20. Advanced Research Deposition System (ARDS) for processing CdTe solar cells

    NASA Astrophysics Data System (ADS)

    Barricklow, Keegan Corey

    CdTe solar cells have been commercialized at the Gigawatt/year level. The development of volume manufacturing processes for next generation CdTe photovoltaics (PV) with higher efficiencies requires research systems with flexibility, scalability, repeatability and automation. The Advanced Research Deposition Systems (ARDS) developed by the Materials Engineering Laboratory (MEL) provides such a platform for the investigation of materials and manufacturing processes necessary to produce the next generation of CdTe PV. Limited by previous research systems, the ARDS was developed to provide process and hardware flexibility, accommodating advanced processing techniques, and capable of producing device quality films. The ARDS is a unique, in-line process tool with nine processing stations. The system was designed, built and assembled at the Materials Engineering Laboratory. Final assembly, startup, characterization and process development are the focus of this research. Many technical challenges encountered during the startup of the ARDS were addressed in this research. In this study, several hardware modifications needed for the reliable operation of the ARDS were designed, constructed and successfully incorporated into the ARDS. The effect of process condition on film properties for each process step was quantified. Process development to achieve 12% efficient baseline solar cell required investigation of discrete processing steps, troubleshooting process variation, and developing performance correlations. Subsequent to this research, many advances have been demonstrated with the ARDS. The ARDS consistently produces devices of 12% +/-.5% by the process of record (POR). The champion cell produced to date utilizing the ARDS has an efficiency of 16.2% on low cost commercial sodalime glass and utilizes advanced films. The ARDS has enabled investigation of advanced concepts for processing CdTe devices including, Plasma Cleaning, Plasma Enhanced Closed Space Sublimation

  1. Synchrotron micro-scale study of trace metal transport and distribution in Spartina alterniflora root system in Yangtze River intertidal zone

    SciTech Connect

    Feng, Huan; Tappero, Ryan; Zhang, Weiguo; Liu, Wenliang; Yu, Lizhong; Qian, Yu; Wang, Jun; Wang, Jia -Jun; Eng, Christopher; Liu, Chang -Jun; Jones, Keith W.

    2015-07-26

    This study is focused on micro-scale measurement of metal (Ca, Cl, Fe, K, Mn, Cu, Pb, and Zn) distributions in Spartina alterniflora root system. The root samples were collected in the Yangtze River intertidal zone in July 2013. Synchrotron X-ray fluorescence (XRF), computed microtomography (CMT), and X-ray absorption near-edge structure (XANES) techniques, which provide micro-meter scale analytical resolution, were applied to this study. Although it was found that the metals of interest were distributed in both epidermis and vascular tissue with the varying concentrations, the results showed that Fe plaque was mainly distributed in the root epidermis. Other metals (e.g., Cu, Mn, Pb, and Zn) were correlated with Fe in the epidermis possibly due to scavenge by Fe plaque. Relatively high metal concentrations were observed in the root hair tip. As a result, this micro-scale investigation provides insights of understanding the metal uptake and spatial distribution as well as the function of Fe plaque governing metal transport in the root system.

  2. Synchrotron micro-scale study of trace metal transport and distribution in Spartina alterniflora root system in Yangtze River intertidal zone

    DOE PAGES

    Feng, Huan; Tappero, Ryan; Zhang, Weiguo; ...

    2015-07-26

    This study is focused on micro-scale measurement of metal (Ca, Cl, Fe, K, Mn, Cu, Pb, and Zn) distributions in Spartina alterniflora root system. The root samples were collected in the Yangtze River intertidal zone in July 2013. Synchrotron X-ray fluorescence (XRF), computed microtomography (CMT), and X-ray absorption near-edge structure (XANES) techniques, which provide micro-meter scale analytical resolution, were applied to this study. Although it was found that the metals of interest were distributed in both epidermis and vascular tissue with the varying concentrations, the results showed that Fe plaque was mainly distributed in the root epidermis. Other metals (e.g.,more » Cu, Mn, Pb, and Zn) were correlated with Fe in the epidermis possibly due to scavenge by Fe plaque. Relatively high metal concentrations were observed in the root hair tip. As a result, this micro-scale investigation provides insights of understanding the metal uptake and spatial distribution as well as the function of Fe plaque governing metal transport in the root system.« less

  3. Synchrotron micro-scale study of trace metal transport and distribution in Spartina alterniflora root system in Yangtze River intertidal zone.

    PubMed

    Feng, Huan; Zhang, Weiguo; Liu, Wenliang; Yu, Lizhong; Qian, Yu; Wang, Jun; Wang, Jia-Jun; Eng, Christopher; Liu, Chang-Jun; Jones, Keith W; Tappero, Ryan

    2015-12-01

    This study is focused on micro-scale measurement of metal (Ca, Cl, Fe, K, Mn, Cu, Pb, and Zn) distributions in Spartina alterniflora root system. The root samples were collected in the Yangtze River intertidal zone in July 2013. Synchrotron X-ray fluorescence (XRF), computed microtomography (CMT), and X-ray absorption near-edge structure (XANES) techniques, which provide micro-meter scale analytical resolution, were applied to this study. Although it was found that the metals of interest were distributed in both epidermis and vascular tissue with the varying concentrations, the results showed that Fe plaque was mainly distributed in the root epidermis. Other metals (e.g., Cu, Mn, Pb, and Zn) were correlated with Fe in the epidermis possibly due to scavenge by Fe plaque. Relatively high metal concentrations were observed in the root hair tip. This micro-scale investigation provides insights of understanding the metal uptake and spatial distribution as well as the function of Fe plaque governing metal transport in the root system.

  4. SPES-2, AP600 intergral system test S01007 2 inch CL to core make-up tank pressure balance line break

    SciTech Connect

    Bacchiani, M.; Medich, C.; Rigamonti, M.

    1995-09-01

    The SPES-2 is a full height, full pressure experimental test facility reproducing the Westinghouse AP600 reactor with a scaling factor of 1/395. The experimental plant, designed and operated by SIET in Piacenza, consists of a full simulation of the AP600 primary core cooling system including all the passive and active safety systems. In 1992, Westinghouse, in cooperation with ENEL (Ente Nazionale per l` Energia Elettrica), ENEA (Enter per le numove Technlogie, l` Energia e l` Ambient), Siet (Societa Informazioni Esperienze Termoidraulich) and ANSALDO developed an experimental program to test the integrated behaviour of the AP600 passive safety systems. The SPES-2 test matrix, concluded in November 1994, has examined the AP600 passive safety system response for a range of small break LOCAs at different locations on the primary system and on the passive system lines; single steam generator tube ruptures with passive and active safety systems and a main steam line break transient to demonstrate the boration capability of passive safety systems for rapid cooldown. Each of the tests has provided detailed experimental results for verification of the capability of the analysis methods to predict the integrated passive safety system behaviour. Cold and hot shakedown tests have been performed on the facility to check the characteristics of the plant before starting the experimental campaign. The paper first presents a description of the SPES-2 test facility then the main results of S01007 test {open_quotes}2{close_quotes} Cold Leg (CL) to Core Make-up Tank (CMT) pressure balance line break{close_quotes} are reported and compared with predictions performed using RELAP5/mod3/80 obtained by ANSALDO through agreement with U.S.N.R.C. (U.S. Nuclear Regulatory Commission). The SPES-2 nodalization and all the calculations here presented were performed by ANSALDO and sponsored by ENEL as a part of pre-test predictions for SPES-2.

  5. Westinghouse Small Modular Reactor nuclear steam supply system design

    SciTech Connect

    Memmott, M. J.; Harkness, A. W.; Van Wyk, J.

    2012-07-01

    generator, and eight reactor coolant pumps (RCP). The containment vessel is 27.1 m (89 ft) long and 9.8 m (32 ft) in diameter, and is designed to withstand pressures up to 1.7 MPa (250 psi). It is completely submerged in a pool of water serving as a heat sink and radiation shield. Housed within the containment are four combined core makeup tanks (CMT)/passive residual heat removal (PRHR) heat exchangers, two in-containment pools (ICP), two ICP tanks and four valves which function as the automatic depressurization system (ADS). The PRHR heat exchangers are thermally connected to two different ultimate heat sink (UHS) tanks which provide transient cooling capabilities. (authors)

  6. The shifting paradigm of Charcot-Marie-Tooth disease.

    PubMed

    Echaniz-Laguna, A

    2015-01-01

    Molecular studies have created a paradigm shift in our perception of Charcot-Marie-Tooth disease (CMT). Indeed, CMT has evolved from the concept of a rather homogeneous hereditary disease exclusively involving peripheral nerves to the concept of a highly heterogeneous clinical and genetic syndrome mainly - but sometimes not exclusively - involving the peripheral nervous system. The phenotypic spectrum of CMT overlaps with other inherited neuropathies such as distal hereditary motor neuropathy (dHMN), hereditary sensory and autonomic neuropathy (HSAN), spinal muscular atrophy (SMA) subtypes, and the neuropathies of mitochondrial disorders. At a molecular level, mutations in one given gene may alternatively provoke CMT, HSAN, dHMN or SMA variants. Over the last years, there have been dramatic advances in deciphering the molecular basis for many CMT subtypes and more than 900 different mutations in more than 60 causative genes are now described. However, as 75% of CMT causative genes apparently remain unknown and as disease-specific therapies are not available, major advances are yet to come in the field of CMT.

  7. Condensation during gravity driven ECC: Experiments with PACTEL

    SciTech Connect

    Munther, R.; Kalli, H.; Kouhia, J.

    1995-09-01

    This paper provides the results of the second series of gravity driven emergency core cooling (ECC) experiments with PACTEL (Parallel Channel Test Loop). The simulated accident was a small break loss-of-coolant accident (SBLOCA) with a break in a cold leg. The ECC flow was provided from a core makeup tank (CMT) located at a higher elevation than the main part of the primary system. The CMT was pressurized with pipings from the pressurizer and a cold leg. The tests indicated that steam condensation in the CMT can prevent ECC and lead to core uncovery.

  8. Application of Automated SEM-EDS Based Mineral Identification Systems to Problems in Metamorphic Petrology

    NASA Astrophysics Data System (ADS)

    Fairhurst, Robert; Barrow, Wendy; Rollinson, Gavyn

    2010-05-01

    Automated scanning electron microscopy-energy dispersive x-ray spectrometer (SEM-EDS) based mineral identification systems such as QEMSCAN have been in development for over 20 years, primarily as a tool to understand mineral liberation and element distribution in metal mining industry. This powerful technique is now being used in non mining applications such as metamorphic petrology where accurate mineral identification and metamorphic fabrics are key to deciphering the metamorphic history of samples. The QEMSCAN was developed by CSIRO for application in the mining industry where it is used to understand mineralogy, texture, mineral associations, the presence of gangue minerals and deleterious elements that may potentially interfere with mineral processing and planning, and the overall impact of mineralogy on grinding and flotation processes. It is capable of identifying most rock-forming minerals in milliseconds from their characteristic x-ray spectra. The collected x-ray spectra are compared to entries in a database containing the species identification profiles (SIPs) and are assigned a label accordingly. QEMSCAN is capable of searching large sample areas at high resolution resulting in the accurate and precise determination of all minerals present. Reports that were originally developed for the mining geologist can be equally useful to the petrologist, e.g. phase/mineral maps, modal mineral abundances and mineral association reports. Identification of key minerals is of great importance to determining the petrologic history of a sample. These key minerals may be few in number and present as small microinclusions (less than 100 μm) making them difficult to identify, if at all, with the petrographic microscope. Therefore, imaging by electron-microprobe or scanning electron microscope are the methods traditionally used. However, because of the small field of view available on these instruments at a magnification necessary to resolve micron sized relicts and

  9. Genetic epidemiology of Charcot-Marie-Tooth disease.

    PubMed

    Braathen, G J

    2012-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system. The frequency of different CMT genotypes has been estimated in clinic populations, but prevalence data from the general population is lacking. Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth disease type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. The CMT phenotype caused by mutation in the myelin protein zero (MPZ) gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P(0) ) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. X-linked Charcot-Marie Tooth disease (CMTX) is caused by mutations in the connexin32 (cx32) gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions. Estimate prevalence of CMT. Estimate frequency of Peripheral Myelin Protein 22 (PMP22) duplication and point mutations, insertions and deletions in Cx32, Early growth response 2 (EGR2), MFN2, MPZ, PMP22 and Small integral membrane protein of lysosome/late endosome (SIMPLE) genes. Description of novel mutations in Cx32, MFN2 and MPZ. Description of de novo mutations in MFN2. Our population based genetic epidemiological survey included persons with CMT residing in eastern Akershus County, Norway. The participants were interviewed and examined by one geneticist/neurologist, and classified clinically, neurophysiologically and genetically. Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included in the MFN2 study. We screened for point mutations in the MFN2 gene. We describe four novel mutations, two in the connexin32 gene and two in the MPZ gene. A total of 245 affected from 116 CMT families from the general population of eastern

  10. Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice.

    PubMed

    Patzkó, Agnes; Bai, Yunhong; Saporta, Mario A; Katona, István; Wu, Xingyao; Vizzuso, Domenica; Feltri, M Laura; Wang, Suola; Dillon, Lisa M; Kamholz, John; Kirschner, Daniel; Sarkar, Fazlul H; Wrabetz, Lawrence; Shy, Michael E

    2012-12-01

    Charcot-Marie-Tooth disease type 1B is caused by mutations in myelin protein zero. R98C mice, an authentic model of early onset Charcot-Marie-Tooth disease type 1B, develop neuropathy in part because the misfolded mutant myelin protein zero is retained in the endoplasmic reticulum where it activates the unfolded protein response. Because oral curcumin, a component of the spice turmeric, has been shown to relieve endoplasmic reticulum stress and decrease the activation of the unfolded protein response, we treated R98C mutant mice with daily gastric lavage of curcumin or curcumin derivatives starting at 4 days of age and analysed them for clinical disability, electrophysiological parameters and peripheral nerve morphology. Heterozygous R98C mice treated with curcumin dissolved in sesame oil or phosphatidylcholine curcumin performed as well as wild-type littermates on a rotarod test and had increased numbers of large-diameter axons in their sciatic nerves. Treatment with the latter two compounds also increased compound muscle action potential amplitudes and the innervation of neuromuscular junctions in both heterozygous and homozygous R98C animals, but it did not improve nerve conduction velocity, myelin thickness, G-ratios or myelin period. The expression of c-Jun and suppressed cAMP-inducible POU (SCIP)-transcription factors that inhibit myelination when overexpressed-was also decreased by treatment. Consistent with its role in reducing endoplasmic reticulum stress, treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin was associated with decreased X-box binding protein (XBP1) splicing. Taken together, these data demonstrate that treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin improves the peripheral neuropathy of R98C mice by alleviating endoplasmic reticulum stress, by reducing the activation of unfolded protein response and by promoting Schwann cell differentiation.

  11. Upper crust response to geodynamic processes beneath Isparta Angle, SW Turkey: Revealed by CMT solutions of earthquakes

    NASA Astrophysics Data System (ADS)

    Över, Semir; Özden, Süha; Kamacı, Züheyr; Yılmaz, Hüseyin; Ünlügenç, Ulvi Can; Pınar, Ali

    2016-09-01

    The Isparta Angle is an important area of SW Anatolia where extensions in all directions (N-S, NE-SW, NW-SE and E-W) meet. These extensions were determined by normal faulting structures as well as by shallow earthquakes. All extensions, except the E-W one, were attributed to the deviatoric stresses in relation to slab forces and/or extrusion of Anatolia. The moment tensor inversion of 40 shallow earthquakes which occurred in the inner part of the Isparta Angle give focal mechanisms mostly indicating normal faulting. Inversion of all focal mechanisms of the earthquakes obtained from the moment tensor inversion yields normal faulting characterized by an approximately E-W (N268°E) σ3 axis. The calculated stress ratio R is 0.6944 indicating a triaxial stress state. Commonly accepted geodynamic models for the eastern Mediterranean region do not include plate boundary forces acting in the east or west direction. Our hypothesis is that the cause of the E-W extension is the combined forces of Gravitational Potential Energy and the hot asthenosphere upwelling through a tear fault in the subducted African plate between the Hellenic and Cyprus arcs beneath the Isparta Angle.

  12. CMT-type beta-lactamase TEM-125, an emerging problem for extended-spectrum beta-lactamase detection.

    PubMed

    Robin, Frédéric; Delmas, Julien; Archambaud, Maryse; Schweitzer, Cédric; Chanal, Catherine; Bonnet, Richard

    2006-07-01

    The clinical strain Escherichia coli TO799 was resistant to penicillin-clavulanate combinations and ceftazidime and was not reproducibly detected as an extended-spectrum beta-lactamase (ESBL) according to the standards of the Clinical Laboratory Standards Institute (CLSI; formerly NCCLS) and the national guidelines of the French Society for Microbiology (Comité de l'Antibiogramme de la Société Française de Microbiologie). A novel beta-lactamase, designated TEM-125, was responsible for this phenotype. TEM-125 harbors a complex association of mutations previously described in the ESBL TEM-12 and in the inhibitor-resistant beta-lactamase TEM-39. TEM-125 is the first complex mutant TEM to present hydrolytic activity against ceftazidime (kcat, 3.7 s(-1)) together with a high level of resistance to clavulanate (50% inhibitory concentration, 13.6 microM). The discovery of such an ESBL, which is difficult to detect by the usual ESBL detection methods, confirms the emergence of a complex mutant TEM subgroup and highlights the need to evaluate detection methods so as to avoid possible therapeutic failures.

  13. Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice

    PubMed Central

    Patzkó, Ágnes; Bai, Yunhong; Saporta, Mario A.; Katona, István; Wu, XingYao; Vizzuso, Domenica; Feltri, M. Laura; Wang, Suola; Dillon, Lisa M.; Kamholz, John; Kirschner, Daniel; Sarkar, Fazlul H.; Wrabetz, Lawrence

    2012-01-01

    Charcot–Marie–Tooth disease type 1B is caused by mutations in myelin protein zero. R98C mice, an authentic model of early onset Charcot–Marie–Tooth disease type 1B, develop neuropathy in part because the misfolded mutant myelin protein zero is retained in the endoplasmic reticulum where it activates the unfolded protein response. Because oral curcumin, a component of the spice turmeric, has been shown to relieve endoplasmic reticulum stress and decrease the activation of the unfolded protein response, we treated R98C mutant mice with daily gastric lavage of curcumin or curcumin derivatives starting at 4 days of age and analysed them for clinical disability, electrophysiological parameters and peripheral nerve morphology. Heterozygous R98C mice treated with curcumin dissolved in sesame oil or phosphatidylcholine curcumin performed as well as wild-type littermates on a rotarod test and had increased numbers of large-diameter axons in their sciatic nerves. Treatment with the latter two compounds also increased compound muscle action potential amplitudes and the innervation of neuromuscular junctions in both heterozygous and homozygous R98C animals, but it did not improve nerve conduction velocity, myelin thickness, G-ratios or myelin period. The expression of c-Jun and suppressed cAMP-inducible POU (SCIP)—transcription factors that inhibit myelination when overexpressed—was also decreased by treatment. Consistent with its role in reducing endoplasmic reticulum stress, treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin was associated with decreased X-box binding protein (XBP1) splicing. Taken together, these data demonstrate that treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin improves the peripheral neuropathy of R98C mice by alleviating endoplasmic reticulum stress, by reducing the activation of unfolded protein response and by promoting Schwann cell differentiation. PMID:23250879

  14. Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis.

    PubMed

    Pehlivan, Davut; Coban Akdemir, Zeynep; Karaca, Ender; Bayram, Yavuz; Jhangiani, Shalini; Yildiz, Edibe Pembegul; Muzny, Donna; Uluc, Kayihan; Gibbs, Richard A; Elcioglu, Nursel; Lupski, James R; Harel, Tamar

    2015-06-01

    Charcot-Marie-Tooth disease is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early-onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum.

  15. Hereditary Motor and Sensory Neuropathy Type VI with Bilateral Middle Cerebellar Peduncle Involvement

    PubMed Central

    Oh, Jung-Hwan; Lee, Han Sang; Cha, Dong Min

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (MFN2) mutation. In patients with MFN2 related CMT, central nervous system is known to be also involved and cerebral white matter is mostly involved. We report a patient confirmed as HMSN VI who had isolated bilateral middle cerebellar peduncular lesions in brain MRI. PMID:25258575

  16. Diagnosis of Charcot-Marie-Tooth Disease

    PubMed Central

    Banchs, Isabel; Casasnovas, Carlos; Albertí, Antonia; De Jorge, Laura; Povedano, Mónica; Montero, Jordi; Martínez-Matos, Juan Antonio; Volpini, Victor

    2009-01-01

    Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN) is a genetically heterogeneous group of conditions that affect the peripheral nervous system. The disease is characterized by degeneration or abnormal development of peripheral nerves and exhibits a range of patterns of genetic transmission. In the majority of cases, CMT first appears in infancy, and its manifestations include clumsiness of gait, predominantly distal muscular atrophy of the limbs, and deformity of the feet in the form of foot drop. It can be classified according to the pattern of transmission (autosomal dominant, autosomal recessive, or X linked), according to electrophysiological findings (demyelinating or axonal), or according to the causative mutant gene. The classification of CMT is complex and undergoes constant revision as new genes and mutations are discovered. In this paper, we review the most efficient diagnostic algorithms for the molecular diagnosis of CMT, which are based on clinical and electrophysiological data. PMID:19826499

  17. Charcot-Marie-Tooth disease type 1: molecular pathogenesis to gene therapy.

    PubMed

    Kamholz, J; Menichella, D; Jani, A; Garbern, J; Lewis, R A; Krajewski, K M; Lilien, J; Scherer, S S; Shy, M E

    2000-02-01

    Charcot-Marie-Tooth disease type 1 (CMT1) is caused by mutations in the peripheral myelin protein, 22 kDa (PMP22) gene, protein zero (P0) gene, early growth response gene 2 (EGR-2) and connexin-32 gene, which are expressed in Schwann cells, the myelinating cells of the peripheral nervous system. Although the clinical and pathological phenotypes of the various forms of CMT1 are similar, including distal muscle weakness and sensory loss, their molecular pathogenesis is likely to be quite distinct. In addition, while demyelination is the hallmark of CMT1, the clinical signs and symptoms of the disease are probably produced by axonal degeneration, not demyelination itself. In this review we discuss the molecular pathogenesis of CMT1, as well as approaches to an effective gene therapy for this disease.

  18. Plasma, cerebrospinal fluid, and brain distribution of /sup 14/C-melatonin in rat: a biochemical and autoradiographic study

    SciTech Connect

    Vitte, P.A.; Harthe, C.; Lestage, P.; Claustrat, B.; Bobillier, P.

    1988-01-01

    The distribution of 14C-Melatonin (14C-MT) after systemic injection was studied in the plasma, cerebrospinal fluid (CSF), and brain of rats. Chromatographic analysis (thin-layer chromatography and high-performance liquid chromatography) indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C-MT. Computer analysis of plasma 14C-MT kinetics showed a three-compartment system with half-lives of 0.21 +/- 0.05, 5.97 +/- 1.11, and 47.52 +/- 8.86 min. The volume of distribution and the clearance were 1,736 +/- 349 ml.kg-1 and 25.1 +/- 1.7 ml.min-1.kg-1 respectively. The entry of 14C-MT into the CSF was rapid and reached a maximum at 5 min. The decay followed a two-compartment system with half-lives of 16.5 +/- 2.9 and 47.3 +/- 8.6 min. The CSF/plasma concentration ratio was 0.38 at the steady state (30 min). At 2 min the level of 14C-MT in the brain was 3.8 higher than in the CSF. Representative autoradiograms revealed an heterogeneous localization of 14C-MT in the grey matter. The highest regional values, as evaluated by the permeability area product technique, were found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb-pons. Thirty minutes later 14C-MT was still detected in most of the brain regions analyzed. These results point to a low but rapid penetration of circulating MT into the brain and the CSF. The heterogeneous distribution and the partial retention of 14C-MT in the brain are compatible with the hypothesis of a central action of this hormone mediated via binding sites.

  19. Solar system positioning system

    NASA Technical Reports Server (NTRS)

    Penanen, Konstantin I.; Chui, Talso

    2006-01-01

    Power-rich spacecraft envisioned in Prometheus initiative open up possibilities for long-range high-rate communication. A constellation of spacecraft on orbits several A.U. from the Sun, equipped with laser transponders and precise clocks can be configured to measure their mutual distances to within few cm. High on-board power can create substantial non-inertial contribution to the spacecraft trajectory. We propose to alleviate this contribution by employing secondary ranging to a passive daughter spacecraft. Such constellation can form the basis of it navigation system capable of providing position information anywhere in the soIar system with similar accuracy. Apart from obvious Solar System exploration implications, this system can provide robust reference for GPS and its successors.

  20. Solar system positioning system

    NASA Technical Reports Server (NTRS)

    Penanen, Konstantin I.; Chui, Talso

    2006-01-01

    Power-rich spacecraft envisioned in Prometheus initiative open up possibilities for long-range high-rate communication. A constellation of spacecraft on orbits several A.U. from the Sun, equipped with laser transponders and precise clocks can be configured to measure their mutual distances to within few cm. High on-board power can create substantial non-inertial contribution to the spacecraft trajectory. We propose to alleviate this contribution by employing secondary ranging to a passive daughter spacecraft. Such constellation can form the basis of it navigation system capable of providing position information anywhere in the soIar system with similar accuracy. Apart from obvious Solar System exploration implications, this system can provide robust reference for GPS and its successors.

  1. Microdisk-waveguide system for the control of the polarization state of light

    NASA Astrophysics Data System (ADS)

    Akhavan, Hooman

    In optical fibers and photonic integrated circuits (PIC's), the signal polarization can undergo random rotations. Since strong confinement (SC) microphotonic devices are polarization sensitive, a chip-scale polarization rotator is beneficial for the realization of chip-scale integrated optics. Moreover, control over polarization states of photon(s) is necessary for realization of quantum information technology in optical domain. Optical microdisks vertically-coupled to a waveguide bus due to the precise control over coupling distance in fabrication and relative ease of dense integration have become increasingly important as a building block for photonic integrated circuits. Both passive and active devices have been demonstrated including channel dropping filters, tunable resonant filters and switches, intensity modulators, phase modulators, laser sources, and WDM demultiplexers. In this research it has been proposed and experimentally observed preferential polarization mode conversion and signal amplification due to the existence of non-zero, asymmetric, and geometry dependent cross-polarization coupling coefficients between non-orthogonal modes of the waveguide and the vertically-coupled active microdisk. A theory based on coupled mode theory (CMT) is developed to realize microdisk-waveguide system as a narrowband polarization rotator. An integrated structure consisting of a polarization splitter, a microdisk as a narrowband polarization rotator and a combiner is proposed to be applicable in fiber communication and integrated optics. A broadband polarization rotator on ridge waveguides was designed. However, it is concluded that microdisk application for a polarization rotator is helpful to reduce the device size at the cost of bandwidth. Tuning of the microdisk resonance is required when the operating wavelength is changed. By incorporation of the two properties of the active microdisk as a polarization rotator and tunable phase shifter, two-microdisk device is

  2. Exploratory Analysis Of The 3D Cloud Resolving Model Simulations of TOGA COARE: Preliminary Results

    NASA Astrophysics Data System (ADS)

    Mendes, S.; Bretherton, C.

    2007-12-01

    Global climate model studies suggest that cumulus momentum transport (CMT) in tropical oceanic convective cloud systems plays a significant role in the tropical mean circulation and transient variability. CMT is difficult to measure directly and can depend on the detailed structure and organization of the convection. Yet there have been comparatively few evaluations of CMT parameterizations and the assumptions underlying them using 3D cloud resolving model (CRM) simulations. We have analyzed CMT in a four month 3D 64x64x64 gridpoint CRM simulation of TOGA COARE with 1 km horizontal resolution. An additional 256x256x64 large-domain simulation was performed for a 10 day subperiod with strong convection combined with substantial mean vertical zonal wind shear, conditions favorably for strong CMT. Both simulations were identically forced with prescribed vertical motion, horizontal temperature and moisture advection, and relaxation of the domain-mean wind profile to observations on a one-hour timescale. Both were initialized with small amplitude white noise, but spun up realistic convection in less than a day. The domain-mean CMT in the small and large domain simulations for the 10-day common simulation period was compared. The two simulations showed remarkably similar CMT profiles on daily-mean timescales, suggesting that mesoscale contributions to CMT of scales greater than 64 km were small. The skill of a downgradient mixing-length parameterization CMT = Mc*L*DU/Dz was also tested. Here , Mc is convective mass flux, dU/dz is mean vertical shear, and L is a mixing length for updraft zonal velocity perturbations associated with entrainment and horizontal pressure gradient accelerations. This was done by regressing CMT at each height was regressed against Mc*DU/Dz at the same height across all 3D model snapshots over the 10 days. The correlation coefficient describes the accuracy of this downgradient parameterization, and L was calculated as the regression slope. In the

  3. Mitochondrial dynamics and inherited peripheral nerve diseases.

    PubMed

    Pareyson, Davide; Saveri, Paola; Sagnelli, Anna; Piscosquito, Giuseppe

    2015-06-02

    Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2 mutations cause CMT type 2A by altering mitochondrial fusion and trafficking along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT type which in most cases is characterized by early onset and rather severe course. GDAP1 mutations also alter fission, fusion and transport of mitochondria and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR-CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its heterozygous mutations lead to early-onset and progressive dominant optic atrophy which may be complicated by other neurological symptoms including peripheral neuropathy. Mutations in several proteins fundamental for the axonal transport or forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT, distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed, mitochondrial transport involves directly or indirectly components of the kinesin superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2), implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such as heat shock proteins (HSPs) also have a fundamental

  4. Muscle spindle alterations precede onset of sensorimotor deficits in Charcot-Marie-Tooth type 2E.

    PubMed

    Villalón, E; Jones, M R; Sibigtroth, C; Zino, S J; Dale, J M; Landayan, D S; Shen, H; Cornelison, D D W; Garcia, M L

    2017-02-01

    Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-L(E396K) ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-L(E396K) mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered. Progression from presymptomatic to symptomatic included a 50% loss of large diameter sensory axons within the fifth lumbar dorsal root of hNF-L(E396K) mice. Owing to proprioceptive deficits and loss of large diameter sensory axons, we analyzed muscle spindle morphology in presymptomatic and symptomatic hNF-L(E396K) and hNF-L control mice. Muscle spindle cross-sectional area and volume were reduced in all hNF-L(E396K) mice analyzed, suggesting that alterations in muscle spindle morphology occurred prior to the onset of typical CMT pathology. These data suggested that CMT2E pathology initiated in the muscle spindles altering the proprioceptive sensory system. Early sensory pathology in CMT2E could provide a unifying hypothesis for the convergence of pathology observed in CMT.

  5. Assessing the environmental performance of construction materials testing using EMS: An Australian study.

    PubMed

    Dejkovski, Nick

    2016-10-01

    This paper reports the audit findings of the waste management practices at 30 construction materials testing (CMT) laboratories (constituting 4.6% of total accredited CMT laboratories at the time of the audit) that operate in four Australian jurisdictions and assesses the organisation's Environmental Management System (EMS) for indicators of progress towards sustainable development (SD). In Australia, waste indicators are 'priority indicators' of environmental performance yet the quality and availability of waste data is poor. National construction and demolition waste (CDW) data estimates are not fully disaggregated and the contribution of CMT waste (classified as CDW) to the national total CDW landfill burden is difficult to quantify. The environmental and human impacts of anthropogenic release of hazardous substances contained in CMT waste into the ecosphere can be measured by construing waste indicators from the EMS. An analytical framework for evaluating the EMS is developed to elucidate CMT waste indicators and assess these indicators against the principle of proportionality. Assessing against this principle allows for: objective evaluations of whether the environmental measures prescribed in the EMS are 'proportionate' to the 'desired' (subjective) level of protection chosen by decision-makers; and benchmarking CMT waste indicators against aspirational CDW targets set by each Australian jurisdiction included in the audit. Construed together, the EMS derived waste indicators and benchmark data provide a composite indicator of environmental performance and progress towards SD. The key audit findings indicate: CMT laboratories have a 'poor' environmental performance (and overall progress towards SD) when EMS waste data are converted into indicator scores and assessed against the principle of proportionality; CMT waste recycling targets are lower when benchmarked against jurisdictional CDW waste recovery targets; and no significant difference in the average

  6. Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

    PubMed Central

    Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H.; Currie, Meagan E.; Norberg, Sara N.; Evsikov, Alexei V.; Miers, Kathy E.; Seburn, Kevin L.; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J.

    2016-01-01

    ABSTRACT Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

  7. Immune System

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Immune System KidsHealth > For Teens > Immune System A A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  8. Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations.

    PubMed

    Sleigh, James N; Dawes, John M; West, Steven J; Wei, Na; Spaulding, Emily L; Gómez-Martín, Adriana; Zhang, Qian; Burgess, Robert W; Cader, M Zameel; Talbot, Kevin; Yang, Xiang-Lei; Bennett, David L; Schiavo, Giampietro

    2017-03-28

    Charcot-Marie-Tooth disease type 2D (CMT2D) is a peripheral nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, housekeeping gene, GARS The mechanisms underlying selective nerve pathology in CMT2D remain unresolved, as does the cause of the mild-to-moderate sensory involvement that distinguishes CMT2D from the allelic disorder distal spinal muscular atrophy type V. To elucidate the mechanism responsible for the underlying afferent nerve pathology, we examined the sensory nervous system of CMT2D mice. We show that the equilibrium between functional subtypes of sensory neuron in dorsal root ganglia is distorted by Gars mutations, leading to sensory defects in peripheral tissues and correlating with overall disease severity. CMT2D mice display changes in sensory behavior concordant with the afferent imbalance, which is present at birth and nonprogressive, indicating that sensory neuron identity is prenatally perturbed and that a critical developmental insult is key to the afferent pathology. Through in vitro experiments, mutant, but not wild-type, GlyRS was shown to aberrantly interact with the Trk receptors and cause misactivation of Trk signaling, which is essential for sensory neuron differentiation and development. Together, this work suggests that both neurodevelopmental and neurodegenerative mechanisms contribute to CMT2D pathogenesis, and thus has profound implications for the timing of future therapeutic treatments.

  9. Continuously moving table time-of-flight angiography of the peripheral veins.

    PubMed

    Huff, Sandra; Honal, Matthias; Baumann, Tobias; Hennig, Jürgen; Markl, Michael; Ludwig, Ute

    2010-05-01

    Time-of-flight (TOF) MR angiography allows for noninvasive vessel imaging. To overcome the limited volumetric coverage of standard TOF techniques, the aim of this study was to investigate the combination of TOF and continuously moving table (CMT) acquisitions for peripheral vein imaging based on image subtraction. Two acquisition strategies are presented: a simple two-step method based on 2-fold CMT acquisition and an advanced one-step method requiring only one continuous scan. Image quality of both CMT TOF techniques was evaluated by semiquantitative image grading and by signal-to-noise ratio and contrast-to-noise ratio analysis for veins of the upper and lower leg in 10 healthy volunteers. Results were compared to a standard stationary two-dimensional (2D) TOF multistation acquisition. Image grading revealed good image quality for both CMT TOF methods, thereby confirming the feasibility of axial 2D CMT TOF to assess the veins of the lower extremities during a single scan. Quantitative evaluation showed no significant difference in signal-to-noise ratio and contrast-to-noise ratio compared to the stationary experiment. Additional measurements in three patients with postthrombotic changes and varicosities demonstrated the clinical applicability of the presented methods. CMT TOF provides promising results and permits the detection of various pathologic changes of the venous system.

  10. Data Systems vs. Information Systems

    PubMed Central

    Amatayakul, Margret K.

    1982-01-01

    This paper examines the current status of “hospital information systems” with respect to the distinction between data systems and information systems. It is proposed that the systems currently existing are incomplete data dystems resulting in ineffective information systems.

  11. Operating Systems.

    ERIC Educational Resources Information Center

    Denning, Peter J.; Brown, Robert L.

    1984-01-01

    A computer operating system spans multiple layers of complexity, from commands entered at a keyboard to the details of electronic switching. In addition, the system is organized as a hierarchy of abstractions. Various parts of such a system and system dynamics (using the Unix operating system as an example) are described. (JN)

  12. Lymph system

    MedlinePlus

    Lymphatic system ... Dains JE, Flynn JA, Solomon BS, Stewart RW. Lymphatic system. In: Ball JW, Dains JE, Flynn JA, Solomon ... 2015:chap 9. Hall JE. The microcirculation and lymphatic system: capillary fluid exchange, interstitial fluid, and lymph flow. ...

  13. Digestive System

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Digestive System KidsHealth > For Parents > Digestive System A A A ... the body can absorb and use. About the Digestive System Almost all animals have a tube-type digestive ...

  14. Two Dynamical System Models Based on Real-World Scenarios: A Swarming Control Model and a Surface Tension Model

    DTIC Science & Technology

    2011-01-01

    Pairwise Potentials.” In Robotics and Automation, 2007 IEEE International Conference on, pp. 2292 –2299, 2007. [CMT03] B. Cook, D. Marthaler, C. Topaz , A...including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing ...Control Model and a Surface Tension Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e

  15. Natural System Mimics: Development and Evaluation of Formation/Decomposition Methods for Methane Hydrate Hosted in Fine Sediments

    NASA Astrophysics Data System (ADS)

    Mahajan, D.; Eaton, M. W.; Kerkar, P.; Jones, K. W.

    2007-05-01

    Marine hydrates constitute a major fraction of the total global hydrate inventory that to date need further characterization. Pristine samples recovered from several marine hydrate sites share a common feature: they invariably show high variability with respect to methane saturation. A fundamental understanding of host sediment characteristics with and without filled hydrates is sought. Previous studies (Winters et al., 2004) show discrepancies between field and laboratory data that was attributed to factors such as different methods used to reform hydrates in the laboratory. Our studies focus on hydrates in fine-grained natural sediments and discerning the effect of methods used to synthesize them under subsurface-mimic conditions. Our integrated approach involves characterization of host sediments by Computed Microtomography (CMT) at a beamline of the National synchrotron Light Source (NSLS) to establish parameters such as porosity and tortuosity on a grain scale of sediments with and without hydrates. The CMT technique is complemented by a recently constructed unit, namely Flexible Integrated Study of Hydrates (FISH) in which one of the pressure vessels is of 200 mL volume and fitted with a 12" sight glass. The vessel mimics hydrate formation under near-surface marine conditions. We have evaluated a sediment sample from the Gulf of Mexico (GOM) recovered during the DOE-JIP cruise. After fractionation, it was classified as Very Fine Silt (< 10 mm) under the Udden-Wentworth particle-size classification scheme. The CMT data collection was followed by charging the sample to the FISH unit and hydrates were formed by the Static method in which gas was periodically charged to maintain the pressure. Pressure dependency was established by conducting three runs at 900, 1200, and 1500 psi for hydrate formation. Results for our CMT and the formation/decomposition kinetics will be discussed. Keywords: Host sediments, sediment-hydrate interaction, methane hydrate, FISH unit

  16. Mechanical Systems

    NASA Technical Reports Server (NTRS)

    Davis, Robert E.

    2002-01-01

    The presentation provides an overview of requirement and interpretation letters, mechanical systems safety interpretation letter, design and verification provisions, and mechanical systems verification plan.

  17. Systems Thinking (and Systems Doing).

    ERIC Educational Resources Information Center

    Brethower, Dale M.; Dams, Peter-Cornelius

    1999-01-01

    Introduces human performance technology (HPT) by answering the following questions related to: what systems does; practical issues and questions to which systems thinking is relevant; research questions and answers with respect to systems thinking; how HPT practitioners can do systems thinking; systems thinking tools; what is and is not known…

  18. Stochastic models for plant microtubule self-organization and structure.

    PubMed

    Eren, Ezgi C; Dixit, Ram; Gautam, Natarajan

    2015-12-01

    One of the key enablers of shape and growth in plant cells is the cortical microtubule (CMT) system, which is a polymer array that forms an appropriately-structured scaffolding in each cell. Plant biologists have shown that stochastic dynamics and simple rules of interactions between CMTs can lead to a coaligned CMT array structure. However, the mechanisms and conditions that cause CMT arrays to become organized are not well understood. It is prohibitively time-consuming to use actual plants to study the effect of various genetic mutations and environmental conditions on CMT self-organization. In fact, even computer simulations with multiple replications are not fast enough due to the spatio-temporal complexity of the system. To redress this shortcoming, we develop analytical models and methods for expeditiously computing CMT system metrics that are related to self-organization and array structure. In particular, we formulate a mean-field model to derive sufficient conditions for the organization to occur. We show that growth-prone dynamics itself is sufficient to lead to organization in presence of interactions in the system. In addition, for such systems, we develop predictive methods for estimation of system metrics such as expected average length and number of CMTs over time, using a stochastic fluid-flow model, transient analysis, and approximation algorithms tailored to our problem. We illustrate the effectiveness of our approach through numerical test instances and discuss biological insights.

  19. Sensitivity and specificity of infrared thermography in detection of subclinical mastitis in dairy cows.

    PubMed

    Polat, B; Colak, A; Cengiz, M; Yanmaz, L E; Oral, H; Bastan, A; Kaya, S; Hayirli, A

    2010-08-01

    The objectives of this experiment were to determine interrelationships among mastitis indicators and evaluate the subclinical mastitis detection ability of infrared thermography (IRT) in comparison with the California Mastitis Test (CMT). Somatic cell count (SCC), CMT, and udder skin surface temperature (USST) data were compiled from 62 Brown Swiss dairy cows (days in milk=117+/-51, milk yield=14.7+/-5.2 kg; mean +/- SD). The CORR, REG, and NLIN procedures of Statistical Analysis System (SAS Institute Inc., Cary, NC) were employed to attain interrelationships among mastitis indicators. The diagnostic merit of IRT as an indirect measure of subclinical mastitis was compared with CMT using the receiver operating characteristics curves. The udder skin surface temperature was positively correlated with the CMT score (r=0.86) and SCC (r=0.73). There was an exponential increase in SCC (SCC, x10(3) cells/mL=22.35 x e(1.31 x CMT score); R(2)=0.98) and a linear increase in USST (USST, degrees C=33.45+1.08 x CMT score; R(2)=0.75) as the CMT score increased. As SCC increased, USST increased logarithmically [USST, degrees C=28.72+0.49 x ln(SCC, x10(3) cells/mL); R(2)=0.72]. The USST for healthy quarters (SCC 400,000 cells/mL; n=135) (mean +/- SE; 33.45+/-0.09 vs. 35.80+/-0.08 degrees C). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value were 95.6, 93.6, 14.97, 0.05, 95.0, and 93.6, respectively, for IRT and 88.9, 98.9, 83.56, 0.11, 99.2, and 86.1, respectively, for CMT. The area under the receiver operating characteristics curve for IRT and CMT was not different. In conclusion, as a noninvasive and quick tool, IRT can be employed for screening subclinical mastitis via measuring USST, with a high predictive diagnostic ability similar to CMT when microbiological culturing is unavailable. However, the

  20. Charcot-Marie-Tooth disease type 2A: from typical to rare phenotypic and genotypic features.

    PubMed

    Bombelli, Francesco; Stojkovic, Tanya; Dubourg, Odile; Echaniz-Laguna, Andoni; Tardieu, Sandrine; Larcher, Kathy; Amati-Bonneau, Patrizia; Latour, Philippe; Vignal, Odile; Cazeneuve, Cécile; Brice, Alexis; Leguern, Eric

    2014-08-01

    disability and an early-onset form and also in patients with later onset. Hydromyelia and spinal cord atrophy support central nervous system involvement in CMT2A.

  1. Source mechanism of the 2014 Aegean Sea earthquake

    NASA Astrophysics Data System (ADS)

    Nakano, Masaru

    2016-04-01

    Rapid determination of centroid moment tensor (CMT) of earthquakes, namely the source centroid location, focal mechanism, and magnitude is important for early disaster responses and issuing Tsunami warnings. In order to evaluate capability of Turkey seismic network for rapid determinations of CMT, I investigate the source mechanism of the 2014 Aegean Sea earthquake (Mw 6.9). Although this event occur out of Turkey seismic network, I obtained stable CMT solution. The CMT solution of this earthquake represents a strike-slip fault, consistent with the geometry of the North Anatolian Fault (NAF), and the source-time function indicates that this event comprised several distinct subevents. Each subevent is considered to have ruptured a different fault segment. This observation indicates the existence of a mechanical barrier, namely a NAF segment boundary, at the hypocenter. I also determined CMT solutions of background seismicity. CMT solutions of background seismicity beneath the Aegean Sea represent strike-slip or normal faulting along the NAF or its branch faults. The tensional axes of these events are oriented northeast-southwest, indicating a transtensional tectonic regime. Beneath the Sea of Marmara, the CMT solutions represent mostly strike-slip faulting, consistent with the motion of the NAF, but we identified a normal fault event with a tensional axis parallel to the strike of the NAF. This mechanism indicates that a pull-apart basin, marking a segment boundary of the NAF, is developing there. Because ruptures of a fault system and large earthquake magnitudes are strongly controlled by the fault system geometry and fault length, mapping fault segments along NAF can help to improve the accuracy of scenarios developed for future disastrous earthquakes in the Marmara region.

  2. Prototype Earthquake Early Warning System for Areas of Highest Seismic Risk in the Western U.S.

    NASA Astrophysics Data System (ADS)

    Bock, Y.; Geng, J.; Goldberg, D.; Saunders, J. K.; Haase, J. S.; Squibb, M. B.; Melgar, D.; Crowell, B. W.; Clayton, R. W.; Yu, E.; Walls, C. P.; Mann, D.; Mencin, D.; Mattioli, G. S.

    2015-12-01

    We report on a prototype earthquake early warning system for the Western U.S. based on GNSS (GPS+GLONASS) observations, and where available collocated GNSS and accelerometer data (seismogeodesy). We estimate with latency of 2-3 seconds GNSS displacement waveforms from more than 120 stations, focusing on the southern segment of the San Andreas fault, the Hayward and Rodgers Creek faults and Cascadia. The displacements are estimated using precise point positioning with ambiguity resolution (PPP-AR), which provides for efficient processing of hundreds of "clients" within the region of interest with respect to a reference frame well outside the expected zone of deformation. The GNSS displacements are useful for alleviating magnitude saturation concerns, rapid earthquake magnitude estimation using peak ground displacements, CMT solutions and finite fault slip models. However, GNSS alone is insufficient for strict earthquake early warning (i.e., P wave detection). Therefore, we employ a self-contained seismogeodetic technique, where collocations of GNSS and accelerometer instruments are available, to estimate real-time displacement and velocity waveforms using PPP-AR with accelerometers (PPP-ARA). Using the velocity waveforms we can detect the P wave arrival for earthquakes of interest (>M 5.5), estimate a hypocenter, S wave propagation, and earthquake magnitude using Pd scaling relationships within seconds. Currently we are gearing up to receive observatory-grade accelerometer data from the CISN. We have deployed 25 inexpensive MEMS accelerometers at existing GNSS stations. The SIO Geodetic Modules that control the flow of the GNSS and accelerometer data are being upgraded with in situ PPP-ARA and P wave picking. In situ processing allows us to use the data at the highest sampling rate of the GNSS receiver (10 Hz or higher), in combination with the 100 Hz accelerometer data. Adding the GLONASS data allows for increased precision in the vertical, an important factor in P

  3. Fluid Management System (FMS) fluid systems overview

    NASA Technical Reports Server (NTRS)

    Baird, R. S.

    1990-01-01

    Viewgraphs on fluid management system (FMS) fluid systems overview are presented. Topics addressed include: fluid management system description including system requirements (integrated nitrogen system, integrated water system, and integrated waste gas system) and physical description; and fluid management system evolution.

  4. Biliary system

    MedlinePlus

    The biliary system creates, moves, stores, and releases bile into the duodenum . This helps the body digest food. It also assists ... from the liver to the duodenum. The biliary system includes: The gallbladder Bile ducts and certain cells ...

  5. Systems thinking.

    PubMed

    Cabrera, Derek; Colosi, Laura; Lobdell, Claire

    2008-08-01

    Evaluation is one of many fields where "systems thinking" is popular and is said to hold great promise. However, there is disagreement about what constitutes systems thinking. Its meaning is ambiguous, and systems scholars have made diverse and divergent attempts to describe it. Alternative origins include: von Bertalanffy, Aristotle, Lao Tsu or multiple aperiodic "waves." Some scholars describe it as synonymous with systems sciences (i.e., nonlinear dynamics, complexity, chaos). Others view it as taxonomy-a laundry list of systems approaches. Within so much noise, it is often difficult for evaluators to find the systems thinking signal. Recent work in systems thinking describes it as an emergent property of four simple conceptual patterns (rules). For an evaluator to become a "systems thinker", he or she need not spend years learning many methods or nonlinear sciences. Instead, with some practice, one can learn to apply these four simple rules to existing evaluation knowledge with transformative results.

  6. Telemetry Systems

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Goddard Space Flight Center developed satellite telemetry processing technology to meet NASA's sophisticated processing requirements. The Microelectronic Systems Branch, a 'company' within Goddard, provided NASA with the telemetry data systems from 1985 to 1994. TSI/Telsys, Inc. was then founded to commercialize the systems and began operations on October 1, 1995. The system aids the remote sensing industry by providing affordable and quick access to data collected from space.

  7. Systems Engineering

    NASA Technical Reports Server (NTRS)

    Pellerano, Fernando

    2015-01-01

    This short course provides information on what systems engineering is and how the systems engineer guides requirements, interfaces with the discipline leads, and resolves technical issues. There are many system-wide issues that either impact or are impacted by the thermal subsystem. This course will introduce these issues and illustrate them with real life examples.

  8. System Effectiveness

    SciTech Connect

    Powell, Danny H; Elwood Jr, Robert H

    2011-01-01

    An effective risk assessment system is needed to address the threat posed by an active or passive insider who, acting alone or in collusion, could attempt diversion or theft of nuclear material. It is critical that a nuclear facility conduct a thorough self-assessment of the material protection, control, and accountability (MPC&A) system to evaluate system effectiveness. Self-assessment involves vulnerability analysis and performance testing of the MPC&A system. The process should lead to confirmation that mitigating features of the system effectively minimize the threat, or it could lead to the conclusion that system improvements or upgrades are necessary to achieve acceptable protection against the threat. Analysis of the MPC&A system is necessary to understand the limits and vulnerabilities of the system to internal threats. Self-assessment helps the facility be prepared to respond to internal threats and reduce the risk of theft or diversion of nuclear material. MSET is a self-assessment or inspection tool utilizing probabilistic risk assessment (PRA) methodology to calculate the system effectiveness of a nuclear facility's MPC&A system. MSET analyzes the effectiveness of an MPC&A system based on defined performance metrics for MPC&A functions based on U.S. and international best practices and regulations. A facility's MC&A system can be evaluated at a point in time and reevaluated after upgrades are implemented or after other system changes occur. The total system or specific subareas within the system can be evaluated. Areas of potential performance improvement or system upgrade can be assessed to determine where the most beneficial and cost-effective improvements should be made. Analyses of risk importance factors show that sustainability is essential for optimal performance. The analyses reveal where performance degradation has the greatest detrimental impact on total system risk and where performance improvements have the greatest reduction in system risk

  9. Cryogenic Systems

    NASA Astrophysics Data System (ADS)

    Hosoyama, Kenji

    2002-02-01

    In this lecture we discuss the principle of method of cooling to a very low temperature, i.e. cryogenic. The "gas molecular model" will be introduced to explain the mechanism cooling by the expansion engine and the Joule-Thomson expansion valve. These two expansion processes are normally used in helium refrigeration systems to cool the process gas to cryogenic temperature. The reverse Carnot cycle will be discussed in detail as an ideal refrigeration cycle. First the fundamental process of liquefaction and refrigeration cycles will be discussed, and then the practical helium refrigeration system. The process flow of the system and the key components; -compressor, expander, and heat exchanger- will be discussed. As an example of an actual refrigeration system, we will use the cryogenic system for the KEKB superconducting RF cavity. We will also discuss the liquid helium distribution system, which is very important, especially for the cryogenic systems used in accelerator applications. 1 Principles of Cooling and Fundamental Cooling Cycle 2 Expansion engine, Joule-Thomson expansion, kinetic molecular theory, and enthalpy 3 Liquefaction Systems 4 Refrigeration Systems 5 Practical helium liquefier/refrigeration system 6 Cryogenic System for TRISTAN Superconducting RF Cavity

  10. Kaiser Permanente's Convergent Medical Terminology.

    PubMed

    Dolin, Robert H; Mattison, John E; Cohn, Simon; Campbell, Keith E; Wiesenthal, Andrew M; Hochhalter, Brad; LaBerge, Diane; Barsoum, Rita; Shalaby, James; Abilla, Alan; Clements, Robert J; Correia, Carol M; Esteva, Diane; Fedack, John M; Goldberg, Bruce J; Gopalarao, Sridhar; Hafeza, Eza; Hendler, Peter; Hernandez, Enrique; Kamangar, Ron; Kahn, Rafique A; Kurtovich, Georgina; Lazzareschi, Gerry; Lee, Moon H; Lee, Tracy; Levy, David; Lukoff, Jonathan Y; Lundberg, Cyndie; Madden, Michael P; Ngo, Trongtu L; Nguyen, Ben T; Patel, Nikhilkumar P; Resneck, Jim; Ross, David E; Schwarz, Kathleen M; Selhorst, Charles C; Snyder, Aaron; Umarji, Mohamed I; Vilner, Max; Zer-Chen, Roy; Zingo, Chris

    2004-01-01

    This paper describes Kaiser Permanente's (KP) enterprise-wide medical terminology solution, referred to as our Convergent Medical Terminology (CMT). Initially developed to serve the needs of a regional electronic health record, CMT has evolved into a core KP asset, serving as the common terminology across all applications. CMT serves as the definitive source of concept definitions for the organization, provides a consistent structure and access method to all codes used by the organization, and is KP's language of interoperability, with cross-mappings to regional ancillary systems and administrative billing codes. The core of CMT is comprised of SNOMED CT, laboratory LOINC, and First DataBank drug terminology. These are integrated into a single poly-hierarchically structured knowledge base. Cross map sets provide bi-directional translations between CMT and ancillary applications and administrative billing codes. Context sets provide subsets of CMT for use in specific contexts. Our experience with CMT has lead us to conclude that a successful terminology solution requires that: (1) usability considerations are an organizational priority; (2) "interface" terminology is differentiated from "reference" terminology; (3) it be easy for clinicians to find the concepts they need; (4) the immediate value of coded data be apparent to clinician user; (5) there be a well defined approach to terminology extensions. Over the past several years, there has been substantial progress made in the domain coverage and standardization of medical terminology. KP has learned to exploit that terminology in ways that are clinician-acceptable and that provide powerful options for data analysis and reporting.

  11. Effect of Cimetidine and Phenobarbital on metabolite kinetics of Omeprazole in rats.

    PubMed

    Park, Eun-Ja; Cho, Hea-Young; Lee, Yong-Bok

    2005-10-01

    Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces the clearance of coadministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance (CLt) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

  12. Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: a laser-evoked potential study.

    PubMed

    Pazzaglia, Costanza; Vollono, Catello; Ferraro, Diana; Virdis, Daniela; Lupi, Valentina; Le Pera, Domenica; Tonali, Pietro; Padua, Luca; Valeriani, Massimiliano

    2010-05-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser-evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient-oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p=0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p>0.05). This result is probably due to a length-dependent Adelta-fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p=0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the Adelta afferents. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Geothermal systems

    NASA Technical Reports Server (NTRS)

    Mohl, C.

    1978-01-01

    Several tasks of JPL related to geothermal energy are discussed. The major task is the procurement and test and evaluation of a helical screw drive (wellhead unit). A general review of geothermal energy systems is given. The presentation focuses attention on geothermal reservoirs in California, with graphs and charts to support the discussion. Included are discussions on cost analysis, systems maintenance, and a comparison of geothermal and conventional heating and cooling systems.

  14. Geothermal systems

    NASA Technical Reports Server (NTRS)

    Mohl, C.

    1978-01-01

    Several tasks of JPL related to geothermal energy are discussed. The major task is the procurement and test and evaluation of a helical screw drive (wellhead unit). A general review of geothermal energy systems is given. The presentation focuses attention on geothermal reservoirs in California, with graphs and charts to support the discussion. Included are discussions on cost analysis, systems maintenance, and a comparison of geothermal and conventional heating and cooling systems.

  15. CALUTRON SYSTEM

    DOEpatents

    Lawrence, E.O.

    1958-08-12

    A calutron system capable of functioning with only a portion of the separation tanks in the system operating is described. The invention is a calutron system comprssing a closed series of alternated tanks and electromagnets having a mid-yoke connecting intermediate positions of the series. dividing the series into twv-o portions, and thereby providing a closed magnetic path through either of the portions.

  16. Systemic Darwinism

    PubMed Central

    Winther, Rasmus Grønfeldt

    2008-01-01

    Darwin's 19th century evolutionary theory of descent with modification through natural selection opened up a multidimensional and integrative conceptual space for biology. We explore three dimensions of this space: explanatory pattern, levels of selection, and degree of difference among units of the same type. Each dimension is defined by a respective pair of poles: law and narrative explanation, organismic and hierarchical selection, and variational and essentialist thinking. As a consequence of conceptual debates in the 20th century biological sciences, the poles of each pair came to be seen as mutually exclusive opposites. A significant amount of 21st century research focuses on systems (e.g., genomic, cellular, organismic, and ecological/global). Systemic Darwinism is emerging in this context. It follows a “compositional paradigm” according to which complex systems and their hierarchical networks of parts are the focus of biological investigation. Through the investigation of systems, Systemic Darwinism promises to reintegrate each dimension of Darwin's original logical space. Moreover, this ideally and potentially unified theory of biological ontology coordinates and integrates a plurality of mathematical biological theories (e.g., self-organization/structure, cladistics/history, and evolutionary genetics/function). Integrative Systemic Darwinism requires communal articulation from a plurality of perspectives. Although it is more general than these, it draws on previous advances in Systems Theory, Systems Biology, and Hierarchy Theory. Systemic Darwinism would greatly further bioengineering research and would provide a significantly deeper and more critical understanding of biological reality. PMID:18697926

  17. Systemic darwinism.

    PubMed

    Winther, Rasmus Grønfeldt

    2008-08-19

    Darwin's 19th century evolutionary theory of descent with modification through natural selection opened up a multidimensional and integrative conceptual space for biology. We explore three dimensions of this space: explanatory pattern, levels of selection, and degree of difference among units of the same type. Each dimension is defined by a respective pair of poles: law and narrative explanation, organismic and hierarchical selection, and variational and essentialist thinking. As a consequence of conceptual debates in the 20th century biological sciences, the poles of each pair came to be seen as mutually exclusive opposites. A significant amount of 21st century research focuses on systems (e.g., genomic, cellular, organismic, and ecological/global). Systemic Darwinism is emerging in this context. It follows a "compositional paradigm" according to which complex systems and their hierarchical networks of parts are the focus of biological investigation. Through the investigation of systems, Systemic Darwinism promises to reintegrate each dimension of Darwin's original logical space. Moreover, this ideally and potentially unified theory of biological ontology coordinates and integrates a plurality of mathematical biological theories (e.g., self-organization/structure, cladistics/history, and evolutionary genetics/function). Integrative Systemic Darwinism requires communal articulation from a plurality of perspectives. Although it is more general than these, it draws on previous advances in Systems Theory, Systems Biology, and Hierarchy Theory. Systemic Darwinism would greatly further bioengineering research and would provide a significantly deeper and more critical understanding of biological reality.

  18. A Review of X-linked Charcot-Marie-Tooth Disease.

    PubMed

    Wang, Ying; Yin, Fei

    2016-05-01

    X-linked Charcot-Marie-Tooth disease (CMTX) is the second common genetic variant of CMT. CMTX type 1 causes 90% of CMTX. The most important clinical features of CMTX are similar with other types of CMT; however, a few patients get the central nervous system involved with or without white matter lesions; males are more severely and earlier affected than females. In this review, the authors focus on the origin and classification of CMTX, the central nervous system manifestations of CMTX1, the possible mechanism by which GJB1 mutations cause CMT1X, and the emerging therapeutic strategies for CMTX. Moreover, several cases are presented to illustrate the central nervous system manifestations.

  19. Anticipatory systems as linguistic systems

    NASA Astrophysics Data System (ADS)

    Ekdahl, Bertil

    2000-05-01

    The idea of system is well established although not well defined. What makes up a system depends on the observer. Thinking in terms of systems is only a convenient way to conceptualize organizations, natural or artificial, that show coherent properties. Among all properties, which can be ascribed to systems, one property seems to be more outstanding than others, namely that of being anticipatory. In nature, anticipatory properties are found only in living organizations. In this way it can be said to separate non-living systems from living because there is no indication that any natural phenomenon occurring in systems where there is no indication of life is anticipatory. The characteristic of living systems is that they are exposed to the evolution contrary to causal systems that do not undergo changes due to the influence of the environment. Causal systems are related to the past in such a way that subsequent situations can be calculated from knowledge of past situations. In causal systems the past is the cause of the present and there is no reference to the future as a determining agent, contrary to anticipatory systems where expectations are the cause of the present action. Since anticipatory properties are characteristic of living systems, this property, as all other properties in living systems, is a result of the evolution and can be found in plants as well as in animals. Thus, it is not only tied to consciousness but is found at a more basic level, i.e., in the interplay between genotype and phenotype. Anticipation is part of the genetic language in such a way that appropriate actions, for events in the anticipatory systems environment, are inscribed in the genes. Anticipatory behavior, as a result of the interpretation of the genetic language, has been selected by the evolution. In this paper anticipatory systems are regarded as linguistic systems and I argue that as such anticipation cannot be fragmented but must be holistically studied. This has the

  20. Educational Systems.

    ERIC Educational Resources Information Center

    Archer, Margaret

    1981-01-01

    Presents a general review of research on educational systems, with emphasis on variations in the definition of an educational system, neglected questions, areas of major concern, research needs, traditional and modern stands in the sociology of education, educational politics, and researcher bias. (DB)

  1. Power system

    DOEpatents

    Hickam, Christopher Dale

    2008-03-18

    A power system includes a prime mover, a transmission, and a fluid coupler having a selectively engageable lockup clutch. The fluid coupler may be drivingly connected between the prime mover and the transmission. Additionally, the power system may include a motor/generator drivingly connected to at least one of the prime mover and the transmission. The power-system may also include power-system controls configured to execute a control method. The control method may include selecting one of a plurality of modes of operation of the power system. Additionally, the control method may include controlling the operating state of the lockup clutch dependent upon the mode of operation selected. The control method may also include controlling the operating state of the motor/generator dependent upon the mode of operation selected.

  2. Phacoemulsification systems.

    PubMed

    1989-11-01

    Our objectives in conducting this evaluation were to present an overview of a basic phacoemulsification system and its components, to describe the phacoemulsification procedure within the context of the operating principles of the system's components, and to compare two manufacturers' products. Specifications for additional phacoemulsification systems are available in the November 1989 edition of ECRI's Hospital Product Comparison System. Both of the evaluated systems enable a surgeon to perform a complete cataract extraction procedure by phacoemulsification. We rated both units Acceptable. In selecting a unit, users should consider performance, safety, human factors design, and manufacturer training and support. Although list prices vary widely among available systems, cost factors should not override clinical performance and safety requirements. While we measured certain engineering parameters, such as stroke length and ultrasound (US) output forces exerted on a medium, we stress that the results of these tests do not provide enough information to predict clinical performance. Clinical performance of phacoemulsification systems can be determined only by the experience of the clinicians who use them. Clinicians should review our evaluation thoroughly before making a purchasing decision. The information we present is useful for purchasing the evaluated or other available models because our criteria will guide users in assessing all components, and our findings and discussion on some aspects are common to many available systems (e.g., type of pump, irrigation and aspiration [I/A] characteristics). The in-depth clinical and technical information will help users to better understand principles, thereby helping them to better define their needs. Although we discovered a number of problems with the evaluated models, users should not assume that similar or other problems do not exist with systems that we did not evaluate. The willingness of manufacturers to cooperate in

  3. Electronic system

    DOEpatents

    Robison, G H; Dickson, J F

    1960-11-15

    An electronic system is designed for indicating the occurrence of a plurality of electrically detectable events within predetermined time intervals. The system comprises separate input means electrically associated with the events under observation an electronic channel associated with each input means, including control means and indicating means; timing means adapted to apply a signal from the input means after a predetermined time to the control means to deactivate each of the channels; and means for resetting the system to its initial condition after the observation of each group of events. (D.L.C.)

  4. Saturn Systems.

    PubMed

    U Rehman, Habib; McKee, Nida A; McKee, Michael L

    2016-01-15

    Several ring systems (Saturn systems) have been studied using DFT methods that include dispersion effects. Comparison with X-ray structures are made with three systems, and the agreement is quite good. Binding enthalpies and binding free energies in dichloromethane and toluene have been computed. The effect of an encapsulated lithium cation is accessed by comparing C60 @(C6 H4 )10 and [Li@C60 @(C6 H4 )10 ](+). The [Li@C60 ](+) cation is a much better acceptor than C60 which leads to greater donor-acceptor interactions and larger charge transfer from the ring to [Li@C60 ](+). © 2015 Wiley Periodicals, Inc.

  5. Systems 2020

    DTIC Science & Technology

    2012-03-22

    SUPPLEMENTARY NOTES 14. ABSTRACT Systems 2020 is the research effort to answer a major portion of the challenge embodied in the DoD?s science and technology...3 ABSTRACT Systems 2020 is the research effort to answer a major portion of the challenge embodied in the DoD’s science and technology priority...DoD’s science and technology priority for Engineered Resilient Systems (ERS). As a follow-on to the SERC’s work in defining technical approaches for

  6. Command system

    NASA Technical Reports Server (NTRS)

    Burow, N. A.; Tam, M. K.

    1982-01-01

    The Multimission Command (MMC) System is described. The major components within the MMC System are discussed, with the emphasis on the telecommunication-related implementations. Two versions of the spacecraft command detection system (the Viking heritage command detector and the NASA standard command detector) are discussed in detail. The former prevails in the existing flight projects and the latter will likely be adopted by the missions of the near future. The preparation of design control tables for the control of command link performance between deep space stations and the spacecraft is also discussed.

  7. Outbreak of subclinical mastitis in a flock of dairy sheep associated with Burkholderia cepacia complex infection.

    PubMed

    Berriatua, E; Ziluaga, I; Miguel-Virto, C; Uribarren, P; Juste, R; Laevens, S; Vandamme, P; Govan, J R

    2001-03-01

    An outbreak of subclinical mastitis in a flock of 620 milking sheep was investigated. Microbiological and epidemiological analyses identified the causative agent as belonging to the Burkholderia cepacia complex (formerly Pseudomonas cepacia). Every ewe in the milking flock was individually tested for subclinical mastitis on two separate occasions, 6 weeks apart, by the California (rapid) mastitis test (CMT). The proportion of CMT-positive ewes was 69 of 393 (17.6%) on the first sampling and 27 of 490 (5.5%) on the second sampling. Pure B. cepacia cultures identified with the API 20 NE system were grown from 64 of 96 (66.7%) CMT-positive ewes and from 1 of 33 (3.0%) CMT-negative ewes. Statistical analysis confirmed the significant association between a positive CMT result and a positive culture result for B. cepacia complex. Additional polyphasic taxonomic analyses of eight isolates showed that seven belonged to B. cepacia genomovar III; the remaining isolate was identified as Burkholderia vietnamiensis (formerly B. cepacia genomovar V). Bacteriological investigation of samples from milking equipment and other environmental sites failed to identify "B. cepacia" in any of the samples taken. To our knowledge, this is the first report of an outbreak of natural infection in animals caused by B. cepacia complex and the first description of B. cepacia complex infection in sheep.

  8. Outbreak of Subclinical Mastitis in a Flock of Dairy Sheep Associated with Burkholderia cepacia Complex Infection

    PubMed Central

    Berriatua, E.; Ziluaga, I.; Miguel-Virto, C.; Uribarren, P.; Juste, R.; Laevens, S.; Vandamme, P.; Govan, J. R. W.

    2001-01-01

    An outbreak of subclinical mastitis in a flock of 620 milking sheep was investigated. Microbiological and epidemiological analyses identified the causative agent as belonging to the Burkholderia cepacia complex (formerly Pseudomonas cepacia). Every ewe in the milking flock was individually tested for subclinical mastitis on two separate occasions, 6 weeks apart, by the California (rapid) mastitis test (CMT). The proportion of CMT-positive ewes was 69 of 393 (17.6%) on the first sampling and 27 of 490 (5.5%) on the second sampling. Pure B. cepacia cultures identified with the API 20 NE system were grown from 64 of 96 (66.7%) CMT-positive ewes and from 1 of 33 (3.0%) CMT-negative ewes. Statistical analysis confirmed the significant association between a positive CMT result and a positive culture result for B. cepacia complex. Additional polyphasic taxonomic analyses of eight isolates showed that seven belonged to B. cepacia genomovar III; the remaining isolate was identified as Burkholderia vietnamiensis (formerly B. cepacia genomovar V). Bacteriological investigation of samples from milking equipment and other environmental sites failed to identify “B. cepacia” in any of the samples taken. To our knowledge, this is the first report of an outbreak of natural infection in animals caused by B. cepacia complex and the first description of B. cepacia complex infection in sheep. PMID:11230416

  9. Steroid-dependent sensorineural hearing loss in a patient with Charcot-Marie-Tooth disease showing auditory neuropathy.

    PubMed

    Maeda, Yukihide; Kataoka, Yuko; Sugaya, Akiko; Kariya, Shin; Kobayashi, Katsuhiro; Nishizaki, Kazunori

    2015-06-01

    Charcot-Marie-Tooth disease (CMT) is the most common form of hereditary sensorimotor neuropathy and sometimes involves disorders of the peripheral auditory system. We present a case of steroid-dependent auditory neuropathy associated with CMT, in which the patient experienced 3 episodes of acute exacerbation of hearing loss and successful rescue of hearing by prednisolone. An 8-year-old boy was referred to the otolaryngology department at the University Hospital. He had been diagnosed with CMT type 1 (demyelinating type) at the Child Neurology Department and was suffering from mild hearing loss due to auditory neuropathy. An audiological diagnosis of auditory neuropathy was confirmed by auditory brainstem response and distortion-product otoacoustic emissions. At 9 years and 0 months old, 9 years and 2 months old, and 10 years and 0 months old, he had experienced acute exacerbations of hearing loss, each of which was successfully rescued by intravenous or oral prednisolone within 2 weeks. Steroid-responsive cases of CMT have been reported, but this is the first case report of steroid-responsive sensorineural hearing loss in CMT. The present case may have implications for the mechanisms of action of glucocorticoids in the treatment of sensorineural hearing loss. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

    PubMed

    Villalón, Eric; Dale, Jeffrey M; Jones, Maria; Shen, Hailian; Garcia, Michael L

    2015-11-19

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.

  11. Molecular Genetics of Charcot-Marie-Tooth Disease: From Genes to Genomes

    PubMed Central

    Azzedine, H.; Senderek, J.; Rivolta, C.; Chrast, R.

    2012-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders of the peripheral nervous system, mainly characterized by distal muscle weakness and atrophy leading to motor handicap. With an estimated prevalence of 1 in 2,500, this condition is one of the most commonly inherited neurological disorders. Mutations in more than 30 genes affecting glial and/or neuronal functions have been associated with different forms of CMT leading to a substantial improvement in diagnostics of the disease and in the understanding of implicated pathophysiological mechanisms. However, recent data from systematic genetic screening performed in large cohorts of CMT patients indicated that molecular diagnosis could be established only in ∼50–70% of them, suggesting that additional genes are involved in this disease. In addition to providing an overview of genetic and functional data concerning various CMT forms, this review focuses on recent data generated through the use of highly parallel genetic technologies (SNP chips, sequence capture and next-generation DNA sequencing) in CMT families, and the current and future impact of these technologies on gene discovery and diagnostics of CMTs. PMID:23293578

  12. Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing.

    PubMed

    Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-31

    Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies.

  13. Molecular genetics of charcot-marie-tooth disease: from genes to genomes.

    PubMed

    Azzedine, H; Senderek, J; Rivolta, C; Chrast, R

    2012-11-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders of the peripheral nervous system, mainly characterized by distal muscle weakness and atrophy leading to motor handicap. With an estimated prevalence of 1 in 2,500, this condition is one of the most commonly inherited neurological disorders. Mutations in more than 30 genes affecting glial and/or neuronal functions have been associated with different forms of CMT leading to a substantial improvement in diagnostics of the disease and in the understanding of implicated pathophysiological mechanisms. However, recent data from systematic genetic screening performed in large cohorts of CMT patients indicated that molecular diagnosis could be established only in ∼50-70% of them, suggesting that additional genes are involved in this disease. In addition to providing an overview of genetic and functional data concerning various CMT forms, this review focuses on recent data generated through the use of highly parallel genetic technologies (SNP chips, sequence capture and next-generation DNA sequencing) in CMT families, and the current and future impact of these technologies on gene discovery and diagnostics of CMTs.

  14. Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing

    PubMed Central

    Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha

    2016-01-01

    Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. PMID:27025386

  15. Counterpoint: long-course chemoradiation is preferable in the neoadjuvant treatment of rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-07-01

    There are 2 approaches to preoperative therapy. Short-course (25 Gy in 5 fractions) radiation and long-course (50.4 Gy in 28 fractions) radiation combined with chemotherapy (CMT). Although short-course radiation therapy is used in some European countries, it is not favored in all European countries or North America. Unlike long-course CMT, it cannot be safely combined with adequate doses of systemic concurrent chemotherapy, and, as currently designed, it does not increase sphincter preservation. Long-course CMT remains the preferred regimen for cT3 and/or node-positive disease. With parallel advances in staging, surgery, systemic therapy, and molecular markers, more selective approaches are being investigated.

  16. Bioculture System

    NASA Technical Reports Server (NTRS)

    Figliozzi, Gianine; Sato, Kevin Y.; Sun. Sidney

    2013-01-01

    The document is a 2 page fact sheet that describes the Bioculture system, how it may be used by researchers for life science research, how and when it will be installed and validated aboard the international space station.

  17. Systems Vaccinology

    PubMed Central

    Pulendran, Bali; Li, Shuzhao; Nakaya, Helder I

    2010-01-01

    Vaccination is one of the greatest triumphs of modern medicine, yet we remain largely ignorant of the mechanisms by which successful vaccines stimulate protective immunity. Two recent advances are beginning to illuminate such mechanisms: realization of the pivotal role of the innate immune system in sensing microbes and stimulating adaptive immunity, and advances in systems biology. Recent studies have used systems biology approaches to obtain a global picture of the immune responses to vaccination in humans. This has enabled the identification of early innate signatures that predict the immunogenicity of vaccines, and identification of potentially novel mechanisms of immune regulation. Here we review these advances, and critically examine the potential opportunities and challenges posed by systems biology in vaccine development. PMID:21029962

  18. Certification Systems

    EPA Pesticide Factsheets

    The WaterSense Product Certification System outlines the process and procedures for the product certification to ensure that all WaterSense labeled products meet EPA's criteria for efficiency and performance.

  19. Compass systems.

    PubMed

    Chernetsov, Nikita

    2017-07-01

    Three compass systems based on global cues known to exist in migrating birds are reviewed. Two of these systems are based on celestial cues, a time-dependent sun compass and time-independent, i.e. not involving the internal clock, star compass. The third system is the magnetic compass, based on a separate sensory modality, which currently attracts much attention from behavioural ecologists, physiologists and physicists. The complex pattern of hierarchy and interactions between these compass systems is briefly discussed. It is argued that rules of integration of information from different compass cues are likely dependent on ecological and geographic conditions the birds are facing during their journey, so it is likely that no single set of rules is shared by all migrating birds.

  20. Respiratory system

    NASA Technical Reports Server (NTRS)

    Bartlett, R. G., Jr.

    1973-01-01

    The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

  1. SAMPLING SYSTEM

    DOEpatents

    Hannaford, B.A.; Rosenberg, R.; Segaser, C.L.; Terry, C.L.

    1961-01-17

    An apparatus is given for the batch sampling of radioactive liquids such as slurries from a system by remote control, while providing shielding for protection of operating personnel from the harmful effects of radiation.

  2. Microelectromechanical Systems

    NASA Technical Reports Server (NTRS)

    Gabriel, Kaigham J.

    1995-01-01

    Micro-electromechanical systems (MEMS) is an enabling technology that merges computation and communication with sensing and actuation to change the way people and machines interact with the physical world. MEMS is a manufacturing technology that will impact widespread applications including: miniature inertial measurement measurement units for competent munitions and personal navigation; distributed unattended sensors; mass data storage devices; miniature analytical instruments; embedded pressure sensors; non-invasive biomedical sensors; fiber-optics components and networks; distributed aerodynamic control; and on-demand structural strength. The long term goal of ARPA's MEMS program is to merge information processing with sensing and actuation to realize new systems and strategies for both perceiving and controlling systems, processes, and the environment. The MEMS program has three major thrusts: advanced devices and processes, system design, and infrastructure.

  3. Fueling systems

    SciTech Connect

    Gorker, G.E.

    1987-01-01

    This report deals with concepts of the Tiber II tokamak reactor fueling systems. Contained in this report are the fuel injection requirement data, startup fueling requirements, intermediate range fueling requirements, power range fueling requirements and research and development considerations. (LSR)

  4. Systems Engineering

    DTIC Science & Technology

    1989-05-01

    evolution of the ultimate contig - ts heavily influenced by the remaining circumstances shown in Pigure 1. Recent policy trends are driving industry towards...which involved the UK Avioni-s Industry in agreeing a weapon system architecture and producing equipment speci- fications. At the same time MBB were...undercarriage indication and monitoring, wheel brakes - enviromental control system including cabin temperature control - engine control and indication

  5. Laser Systems

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Tunable diode lasers are employed as radiation sources in high resolution infrared spectroscopy to determine spectral characteristics of gaseous compounds. With other laser systems, they are produced by Spectra-Physics, and used to monitor chemical processes, monitor production of quantity halogen lamps, etc. The Laser Analytics Division of Spectra-Physics credits the system's reliability to a program funded by Langley in the 1970s. Company no longer U.S.-owned. 5/22/97

  6. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  7. Systems Studies

    SciTech Connect

    Graham, R.L.

    1998-03-17

    The Systems Studies Activity had two objectives: (1) to investigate nontechnical barriers to the deployment of biomass production and supply systems and (2) to enhance and extend existing systems models of bioenergy supply and use. For the first objective, the Activity focused on existing bioenergy markets. Four projects were undertaken: a comparative analysis of bioenergy in Sweden and Austria; a one-day workshop on nontechnical barriers jointly supported by the Production Systems Activity; the development and testing of a framework for analyzing barriers and drivers to bioenergy markets; and surveys of wood pellet users in Sweden, Austria and the US. For the second objective, two projects were undertaken. First, the Activity worked with the Integrated BioEnergy Systems (TBS) Activity of TEA Bioenergy Task XIII to enhance the BioEnergy Assessment Model (BEAM). This model is documented in the final report of the IBS Activity. The Systems Studies Activity contributed to enhancing the feedstock portion of the model by developing a coherent set of willow, poplar, and switchgrass production modules relevant to both the US and the UK. The Activity also developed a pretreatment module for switchgrass. Second, the Activity sponsored a three-day workshop on modeling bioenergy systems with the objectives of providing an overview of the types of models used to evaluate bioenergy and promoting communication among bioenergy modelers. There were nine guest speakers addressing different types of models used to evaluate different aspects of bioenergy, ranging from technoeconomic models based on the ASPEN software to linear programming models to develop feedstock supply curves for the US. The papers from this workshop have been submitted to Biomass and Bioenergy and are under editorial review.

  8. Space Systems - Flight Pressurized Systems

    DTIC Science & Technology

    2009-06-03

    Hazard: An existing or potential condition that can result in an accident. Hydrogen Embrittlement : A mechanical-environmental failure process that...environments. Materials which are susceptible to stress- corrosion cracking or hydrogen embrittlement shall be evaluated by performing sustained-load...Oxygen and Oxygen Systems NSS 1740.16 NASA Safety Standard for Hydrogen and Hydrogen Systems SMC-TR-06-11 (AKA TR-2004

  9. Systemic fluoride.

    PubMed

    Sampaio, Fábio Correia; Levy, Steven Marc

    2011-01-01

    There is substantial evidence that fluoride, through different applications and formulas, works to control caries development. The first observations of fluoride's effects on dental caries were linked to fluoride naturally present in the drinking water, and then from controlled water fluoridation programs. Other systemic methods to deliver fluoride were later suggested, including dietary fluoride supplements such as salt and milk. These systemic methods are now being questioned due to the fact that many studies have indicated that fluoride's action relies mainly on its post-eruptive effect from topical contact with the tooth structure. It is known that even the methods of delivering fluoride known as 'systemic' act mainly through a topical effect when they are in contact with the teeth. The effectiveness of water fluoridation in many geographic areas is lower than in previous eras due to the widespread use of other fluoride modalities. Nevertheless, this evidence should not be interpreted as an indication that systemic methods are no longer relevant ways to deliver fluoride on an individual basis or for collective health programs. Caution must be taken to avoid excess ingestion of fluoride when prescribing dietary fluoride supplements for children in order to minimize the risk of dental fluorosis, particularly if there are other relevant sources of fluoride intake - such as drinking water, salt or milk and/or dentifrice. Safe and effective doses of fluoride can be achieved when combining topical and systemic methods.

  10. Systemic trauma.

    PubMed

    Goldsmith, Rachel E; Martin, Christina Gamache; Smith, Carly Parnitzke

    2014-01-01

    Substantial theoretical, empirical, and clinical work examines trauma as it relates to individual victims and perpetrators. As trauma professionals, it is necessary to acknowledge facets of institutions, cultures, and communities that contribute to trauma and subsequent outcomes. Systemic trauma-contextual features of environments and institutions that give rise to trauma, maintain it, and impact posttraumatic responses-provides a framework for considering the full range of traumatic phenomena. The current issue of the Journal of Trauma & Dissociation is composed of articles that incorporate systemic approaches to trauma. This perspective extends conceptualizations of trauma to consider the influence of environments such as schools and universities, churches and other religious institutions, the military, workplace settings, hospitals, jails, and prisons; agencies and systems such as police, foster care, immigration, federal assistance, disaster management, and the media; conflicts involving war, torture, terrorism, and refugees; dynamics of racism, sexism, discrimination, bullying, and homophobia; and issues pertaining to conceptualizations, measurement, methodology, teaching, and intervention. Although it may be challenging to expand psychological and psychiatric paradigms of trauma, a systemic trauma perspective is necessary on both scientific and ethical grounds. Furthermore, a systemic trauma perspective reflects current approaches in the fields of global health, nursing, social work, and human rights. Empirical investigations and intervention science informed by this paradigm have the potential to advance scientific inquiry, lower the incidence of a broader range of traumatic experiences, and help to alleviate personal and societal suffering.

  11. Turbine system

    DOEpatents

    McMahan, Kevin Weston; Dillard, Daniel Jackson

    2016-05-03

    A turbine system is disclosed. The turbine system includes a transition duct having an inlet, an outlet, and a passage extending between the inlet and the outlet and defining a longitudinal axis, a radial axis, and a tangential axis. The outlet of the transition duct is offset from the inlet along the longitudinal axis and the tangential axis. The turbine system further includes a turbine section connected to the transition duct. The turbine section includes a plurality of shroud blocks at least partially defining a hot gas path, a plurality of buckets at least partially disposed in the hot gas path, and a plurality of nozzles at least partially disposed in the hot gas path. At least one of a shroud block, a bucket, or a nozzle includes means for withstanding high temperatures.

  12. Robotic System

    NASA Technical Reports Server (NTRS)

    1984-01-01

    A complicated design project, successfully carried out by New York manufacturing consultant with help from NERAC, Inc., resulted in new type robotic system being marketed for industrial use. Consultant Robert Price, operating at E.S.I, Inc. in Albany, NY, sought help from NERAC to develop an automated tool for deburring the inside of 8 inch breech ring assemblies for howitzers produced by Watervliet Arsenal. NERAC conducted a search of the NASA data base and six others. From information supplied, Price designed a system consisting of a standard industrial robot arm, with a specially engineered six-axis deburring tool fitted to it. A microcomputer and computer program direct the tool on its path through the breech ring. E.S.I. markets the system to aerospace and metal cutting industries for deburring, drilling, routing and refining machined parts.

  13. Complex Systems

    PubMed Central

    Goldberger, Ary L.

    2006-01-01

    Physiologic systems in health and disease display an extraordinary range of temporal behaviors and structural patterns that defy understanding based on linear constructs, reductionist strategies, and classical homeostasis. Application of concepts and computational tools derived from the contemporary study of complex systems, including nonlinear dynamics, fractals and “chaos theory,” is having an increasing impact on biology and medicine. This presentation provides a brief overview of an emerging area of biomedical research, including recent applications to cardiopulmonary medicine and chronic obstructive lung disease. PMID:16921107

  14. ELECTRONIC SYSTEM

    DOEpatents

    Robison, G.H. et al.

    1960-11-15

    An electronic system is described for indicating the occurrence of a plurality of electrically detectable events within predetermined time intervals. It is comprised of separate input means electrically associated with the events under observation: an electronic channel associated with each input means including control means and indicating means; timing means associated with each of the input means and the control means and adapted to derive a signal from the input means and apply it after a predetermined time to the control means to effect deactivation of each of the channels; and means for resetting the system to its initial condition after observation of each group of events.

  15. Microbiology System

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Technology originating in a NASA-sponsored study of the measurement of microbial growth in zero gravity led to the development of Biomerieux Vitek, Inc.'s VITEK system. VITEK provides a physician with accurate diagnostic information and identifies the most effective medication. Test cards are employed to identify organisms and determine susceptibility to antibiotics. A photo-optical scanner scans the card and monitors changes in the growth of cells contained within the card. There are two configurations - VITEK and VITEK JR as well as VIDAS, a companion system that detects bacteria, viruses, etc. from patient specimens. The company was originally created by McDonnell Douglas, the NASA contractor.

  16. Computer systems

    NASA Technical Reports Server (NTRS)

    Olsen, Lola

    1992-01-01

    In addition to the discussions, Ocean Climate Data Workshop hosts gave participants an opportunity to hear about, see, and test for themselves some of the latest computer tools now available for those studying climate change and the oceans. Six speakers described computer systems and their functions. The introductory talks were followed by demonstrations to small groups of participants and some opportunities for participants to get hands-on experience. After this familiarization period, attendees were invited to return during the course of the Workshop and have one-on-one discussions and further hands-on experience with these systems. Brief summaries or abstracts of introductory presentations are addressed.

  17. Neuromodulatory systems

    PubMed Central

    Werner, Gerhard; Mitterauer, Bernhard J.

    2013-01-01

    We examine the interactions and interdependencies between Neuroglia, the Brain-Cell Microenvironment, and the processes commonly subsumed under Neuromodulation. The interactions of the component processes covering a wide spectrum of frequencies are designated as Neuromodulatory Systems (NMS). This implies NMS's scale-invariance as the capacity of linking actions across many time scales, and self-similarity at any scale. These features endow NMS with the ability to respond adaptively to neural impulse traffic of an unpredictably wide frequency spectrum. In this preliminary perspective, the components of NMS are only outlined based on concepts of Complex Systems Dynamics. However, their interactions must be formally elaborated in further investigations. PMID:23532509

  18. Congenital muscular torticollis in older children: treatment with Z-plasty technique.

    PubMed

    Ekici, Nur Yucel; Kizilay, Ahmet; Akarcay, Mustafa; Firat, Yezdan

    2014-09-01

    Congenital muscular torticollis (CMT) is a common congenital disorder of the musculoskeletal system in neonates and infants. The aim of this study was to evaluate the results of inferior Z-plasty in older children with CMT. They had mean age of 10 years (range, 5-14 years) and were followed up for 1 to 6 years. Postoperative protocol included a neck exercise program composed of active and passive movements in all cases and immobilization with a cervical collar in only 4 patients. This study concluded that surgical management of older children with CMT using Z-lengthening gives excellent clinical and functional results. The procedure is much more effective than other techniques and relatively complication-free and safe. Postoperative cervical collar and a well-planed physiotherapy protocol go a long way toward ensuring good to excellent results. Early diagnosis and treatment are necessary for good results.

  19. Analysis of the AP600 core makeup tank experiments using the NOTRUMP code

    SciTech Connect

    Cunningham, J.C.; Haberstroh, R.C.; Hochreiter, L.E.; Jaroszewicz, J.

    1995-12-31

    The AP600 design utilizes passive methods to perform core and containment cooling functions for a postulated loss of coolant. The core makeup tank (CMT) is an important feature of the AP600 passive safety system. The NOTRUMP code has been compared to the 300-series core makeup tank experiments. It has been observed that the code will capture the correct thermal-hydraulic behavior observed in the experiments. The correlations used for wall film condensation and convective heat transfer to the heated CMT liquid appear to be appropriate for these applications. The code will predict the rapid condensation and mixing thermal-hydraulic behavior observed in the 300-series tests. The NOTRUMP predictions can be noding-dependent since the condensation is extremely dependent on the amount of cold CMT liquid that mixes with the incoming steam flow.

  20. Domain Organization and Active Site Architecture of a Polyketide Synthase C-methyltransferase.

    PubMed

    Skiba, Meredith A; Sikkema, Andrew P; Fiers, William D; Gerwick, William H; Sherman, David H; Aldrich, Courtney C; Smith, Janet L

    2016-12-16

    Polyketide metabolites produced by modular type I polyketide synthases (PKS) acquire their chemical diversity through the variety of catalytic domains within modules of the pathway. Methyltransferases are among the least characterized of the catalytic domains common to PKS systems. We determined the domain boundaries and characterized the activity of a PKS C-methyltransferase (C-MT) from the curacin A biosynthetic pathway. The C-MT catalyzes S-adenosylmethionine-dependent methyl transfer to the α-position of β-ketoacyl substrates linked to acyl carrier protein (ACP) or a small-molecule analog but does not act on β-hydroxyacyl substrates or malonyl-ACP. Key catalytic residues conserved in both bacterial and fungal PKS C-MTs were identified in a 2 Å crystal structure and validated biochemically. Analysis of the structure and the sequences bordering the C-MT provides insight into the positioning of this domain within complete PKS modules.

  1. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  2. System Dynamics

    NASA Astrophysics Data System (ADS)

    Morecroft, John

    System dynamics is an approach for thinking about and simulating situations and organisations of all kinds and sizes by visualising how the elements fit together, interact and change over time. This chapter, written by John Morecroft, describes modern system dynamics which retains the fundamentals developed in the 1950s by Jay W. Forrester of the MIT Sloan School of Management. It looks at feedback loops and time delays that affect system behaviour in a non-linear way, and illustrates how dynamic behaviour depends upon feedback loop structures. It also recognises improvements as part of the ongoing process of managing a situation in order to achieve goals. Significantly it recognises the importance of context, and practitioner skills. Feedback systems thinking views problems and solutions as being intertwined. The main concepts and tools: feedback structure and behaviour, causal loop diagrams, dynamics, are practically illustrated in a wide variety of contexts from a hot water shower through to a symphony orchestra and the practical application of the approach is described through several real examples of its use for strategic planning and evaluation.

  3. Colloidal System

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This colloidal system is a model used to study the fundamentals of solidification. A colloidal mixture of hard spheres dispersed in a liquid has started to form crystals. As the crystallites grow on earth they become heavier and fall to the bottom of the liquid, which disturbs their growth. When grown in microgravity the crystallites remain suspended in the liquid and grow much larger.

  4. Anesthesia systems.

    PubMed

    2006-07-01

    This Evaluation presents ECRI's detailed findings for three newly tested anesthesia systems and updated ratings for three previously evaluated ones. The study focuses on models intended for the full range of inpatient surgical applications. That is, we consider whether and how well the systems--three supplied by Datex-Ohmeda and three supplied by Draeger Medical--can meet the needs of patients covering a wide range of ages, sizes, and conditions. We also consider the adequacy of the systems' safety features, the comprehensiveness of their pre-use checks, and ease of use. We found that all the evaluated units generally perform well, displaying comparable accuracy and consistency of delivery when similarly equipped (e.g., with comparable ventilation modes). However, all the systems also have critical limitations associated with their pre-use check procedures. Several units also exhibit problems with the handling of important alarms under certain conditions. Our ratings will help guide healthcare facilities both when selecting a model and when determining which options to purchase. In several cases, models that are otherwise appropriate for use are rated Not Recommended for purchase if they are not equipped with certain options. And in one case, we rate a unit Unacceptable for purchase if it is not equipped with a safety feature that can help reduce the risk of surgical fires.

  5. Cardiovascular system

    MedlinePlus Videos and Cool Tools

    ... and essential nutrients to all of the living cells in the body, and also carries waste products from the tissues to the systems of the body through which they are eliminated. Most of the ... of red and white blood cells, and other solid elements called platelets.

  6. Instructional Systems.

    ERIC Educational Resources Information Center

    Banathy, Bela H.

    The underlying assumption of this book is that the systems approach has a dual role in education. "As applied 'in' education, it offers a powerful methodology for decisionmaking and design development. As applied 'to' education, it may bring about a clear understanding of what education is truly about." The essential purpose of the book is to…

  7. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  8. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  9. Dissipative systems.

    NASA Technical Reports Server (NTRS)

    Lasalle, J. P.

    1972-01-01

    A theory is presented that shows how the concept of dissipative systems of ordinary differential equations can be extended to include a broad class of functional and partial differential equations, such as retarded functional differential equations and parabolic partial differential equations. Since the basic hypotheses are all in terms of boundedness, finding sufficient conditions in terms of Liapunov functions would not be too difficult.

  10. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  11. International Systems.

    ERIC Educational Resources Information Center

    Saba, Farhad, Ed.

    1999-01-01

    Completes a discussion of a systems model of distance education (in articles since May 1999) focusing on the most complex level, international. Discussion includes transfer of technology from United States universities to developing nations, the free market, and the age of the global economy. Presents a list of "early indicators" of changes in…

  12. Systems Science

    ERIC Educational Resources Information Center

    Christakis, Alexander; Hammond, Debora; Jackson, Michael; Laszlo, Alexander; Mitroff, Ian; Snowden, Dave; Troncale, Len; Carr-Chellman, Alison; Spector, J. Michael; Wilson, Brent

    2013-01-01

    Scholars representing the field of systems science were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Alexander Christakis, Debora Hammond, Michael Jackson, Alexander Laszlo, Ian Mitroff, Dave…

  13. Systems Science

    ERIC Educational Resources Information Center

    Christakis, Alexander; Hammond, Debora; Jackson, Michael; Laszlo, Alexander; Mitroff, Ian; Snowden, Dave; Troncale, Len; Carr-Chellman, Alison; Spector, J. Michael; Wilson, Brent

    2013-01-01

    Scholars representing the field of systems science were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Alexander Christakis, Debora Hammond, Michael Jackson, Alexander Laszlo, Ian Mitroff, Dave…

  14. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

    PubMed Central

    2009-01-01

    Background High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-Tooth type 1A patients and whether this treatment is safe. Methods Patients below age 25 years were randomly assigned to receive placebo or ascorbic acid (one gram twice daily) in a double-blind fashion during one year. The primary outcome measure was the change over time in motor nerve conduction velocity of the median nerve. Secondary outcome measures included changes in minimal F response latencies, compound muscle action potential amplitude, muscle strength, sensory function, Charcot-Marie-Tooth neuropathy score, and disability. Results There were no significant differences between the six placebo-treated (median age 16 years, range 13 to 24) and the five ascorbic acid-treated (19, 14 to 24) patients in change in motor nerve conduction velocity of the median nerve (mean difference ascorbic acid as opposed to placebo treatment of 1.3 m/s, confidence interval -0.3 to 3.0 m/s, P = 0.11) or in change of any of the secondary outcome measures over time. One patient in the ascorbic acid group developed a skin rash, which led to discontinuation of the study medication. Conclusion Oral high dose ascorbic acid for one year did not improve myelination of the median nerve in young Charcot-Marie-Tooth type 1A patients. Treatment was relatively safe. Trial registration Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635. PMID:19909499

  15. Systems Chronotherapeutics

    PubMed Central

    Innominato, Pasquale F.; Dallmann, Robert; Rand, David A.; Lévi, Francis A.

    2017-01-01

    Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are controlled by the circadian timing system. Thus, the tolerability of nearly 500 medications varies by up to fivefold according to circadian scheduling, both in experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved the circadian timing system as a function of drug timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated in randomized clinical trials, especially for cancer and inflammatory diseases. However, recent technological advances have highlighted large interpatient differences in circadian functions resulting in significant variability in chronotherapy response. Such findings advocate for the advancement of personalized chronotherapeutics through interdisciplinary systems approaches. Thus, the combination of mathematical, statistical, technological, experimental, and clinical expertise is now shaping the development of dedicated devices and diagnostic and delivery algorithms enabling treatment individualization. In particular, multiscale systems chronopharmacology approaches currently combine mathematical modeling based on cellular and whole-body physiology to preclinical and clinical investigations toward the design of patient-tailored chronotherapies. We review recent systems research works aiming to the individualization of disease treatment, with emphasis on both cancer management and circadian timing system–resetting strategies for improving chronic disease control and

  16. Analysis of the preliminary results based on the first source solutions for the 29th September 2009 Samoan tsunami: hints for a tsunami early warning system strategy

    NASA Astrophysics Data System (ADS)

    Tinti, Stefano; Armigliato, Alberto; Tonini, Roberto

    2010-05-01

    The 29 September 2009 Samoan tsunami was triggered by a strong earthquake (Mw=8.1) that occurred at 17:48 UTC offshore south of Samoa Islands. This earthquake represents an example of the so-called "outer-rise" earthquakes, that occur in the subducting plate before it enters in the subduction zone and their fault mechanism is normal instead of thrust as expected inside the subduction zone. The areas most affected were the south coasts of Western and American Samoa, where maximum peak-to-peak height of about 3.5 meters and 1.5 meters were recorded by tide-gauge stations respectively at Pago-Pago (American Samoa) and at Apia (Western Samoa). Almost 200 persons were killed and run-up heights were measured in excess of 5 meters on several locations along the coast. This "anomalous" event is considered here "a posteriori" as a good case to test (and to open a discussion on) the today strategies used to forecast tsunami characteristics in the frame of Tsunami Early Warning Systems. In this work different fault models based on the focal mechanism solution proposed by Harvard CMT and USGS immediately after the 2009 Samoan earthquake are considered and tested by comparing some recorded signals (three offshore DART buoys and the two coastal tide gauges located at Apia and Pago-Pago) to the synthetic signals resulting from the numerical simulations provided by the UBO-TSUFD code, that is developed and maintained by the Tsunami Research Team of Bologna University. The analysis found out that all the considered sources lead to some discrepancies between observed and computed signals, though some of them reproduce some of the records quite well. These results suggest some important considerations on the tsunami forecast methods as well as on the difficulty and need of issuing timely and reliable warning in case of complex hazardous situation, which is a task that may require sophisticated decision-making platforms. This work has been conducted in the frame of the European

  17. Imaging diagnosis--celiacomesenteric trunk and portal vein hypoplasia in a pit bull terrier.

    PubMed

    Ricciardi, Mario; Martino, Rosmara; Assad, Eyad Abu

    2014-01-01

    The computed tomography (CT) imaging findings of a celiacomesenteric trunk (CMT) in a 1-year-old dog with primary hypoplasia of the portal vein (PHPV) are described. Computed tomography angiography revealed acquired porto-systemic shunts secondary to portal hypertension and a common origin of the celiac and cranial mesenteric arteries. The imaging findings and the association of a CMT with other vascular diseases have never been reported in dogs. The recognition of this rare arterial anomaly should prompt to investigate possible concurrent vascular diseases and may influence the planning of abdominal surgeries.

  18. Solar Systems

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The solar collectors shown are elements of domestic solar hot water systems produced by Solar One Ltd., Virginia Beach, Virginia. Design of these systems benefited from technical expertise provided Solar One by NASA's Langley Research Center. The company obtained a NASA technical support package describing the d e sign and operation of solar heating equipment in NASA's Tech House, a demonstration project in which aerospace and commercial building technology are combined in an energy- efficient home. Solar One received further assistance through personal contact with Langley solar experts. The company reports that the technical information provided by NASA influenced Solar One's panel design, its selection of a long-life panel coating which increases solar collection efficiency, and the method adopted for protecting solar collectors from freezing conditions.

  19. Burner systems

    DOEpatents

    Doherty, Brian J.

    1984-07-10

    A burner system particularly useful for downhole deployment includes a tubular combustion chamber unit housed within a tubular coolant jacket assembly. The combustion chamber unit includes a monolithic tube of refractory material whose inner surface defines the combustion zone. A metal reinforcing sleeve surrounds and extends the length of the refractory tube. The inner surface of the coolant jacket assembly and outer surface of the combustion chamber unit are dimensioned so that those surfaces are close to one another in standby condition so that the combustion chamber unit has limited freedom to expand with that expansion being stabilized by the coolant jacket assembly so that compression forces in the refractory tube do not exceed about one-half the safe compressive stress of the material; and the materials of the combustion chamber unit are selected to establish thermal gradient parameters across the combustion chamber unit to maintain the refractory tube in compression during combustion system start up and cool down sequences.

  20. Surveying System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Sunrise Geodetic Surveys are setting up their equipment for a town survey. Their equipment differs from conventional surveying systems that employ transit rod and chain to measure angles and distances. They are using ISTAC Inc.'s Model 2002 positioning system, which offers fast accurate surveying with exceptional signals from orbiting satellites. The special utility of the ISTAC Model 2002 is that it can provide positioning of the highest accuracy from Navstar PPS signals because it requires no knowledge of secret codes. It operates by comparing the frequency and time phase of a Navstar signal arriving at one ISTAC receiver with the reception of the same set of signals by another receiver. Data is computer processed and translated into three dimensional position data - latitude, longitude and elevation.

  1. Copernican System

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    The heliocentric (i.e. `Sun-centered') theory proposed by the Polish astronomer Nicolaus Copernicus (1473-1543), and published by him in 1543 in his book, De Revolutionibus Orbium Coelestium. In this system Copernicus placed the Sun at the center of the universe and regarded the Earth and the planets as moving around it in circular orbits. Because of his retention of the notion of circular motion...

  2. Propulsion Systems

    DTIC Science & Technology

    2011-03-31

    6. Conduct Trade Studies Choose a baseline propulsion system Document trade results and the reasons for those results. Iterate the process as...control of electrical power (typically 1-5 kW, but modules of 30 kW have been flown [Cassidy, 2002]) is expensive. The regular obsolescence of...has long focused on MPD thrusters, which scale best for power levels above 100 kW. Metal propellants such as lithium have been proposed [ Tikhonov

  3. Gasification system

    DOEpatents

    Haldipur, Gaurang B.; Anderson, Richard G.; Cherish, Peter

    1983-01-01

    A method and system for injecting coal and process fluids into a fluidized bed gasification reactor. Three concentric tubes extend vertically upward into the fluidized bed. Coal particulates in a transport gas are injected through an inner tube, and an oxygen rich mixture of oxygen and steam are injected through an inner annulus about the inner tube. A gaseous medium relatively lean in oxygen content, such as steam, is injected through an annulus surrounding the inner annulus.

  4. Gasification system

    DOEpatents

    Haldipur, Gaurang B.; Anderson, Richard G.; Cherish, Peter

    1985-01-01

    A method and system for injecting coal and process fluids into a fluidized bed gasification reactor. Three concentric tubes extend vertically upward into the fluidized bed. Coal particulates in a transport gas are injected through an inner tube, and an oxygen rich mixture of oxygen and steam are injected through an inner annulus about the inner tube. A gaseous medium relatively lean in oxygen content, such as steam, is injected through an annulus surrounding the inner annulus.

  5. Dissipative systems

    NASA Technical Reports Server (NTRS)

    Lasalle, J. P.

    1971-01-01

    The abstract theory presented shows how the theory of dissipative systems of ordinary differential equations can be extended to include a wide class of functional and partial differential equations. Since the basic hypotheses are all in terms of boundedness, finding sufficient conditions in terms of Liapunov functions was not difficult. Work is being undertaken to solve some nontrivial examples to illustrate how the theory can applied.

  6. Security system

    DOEpatents

    Baumann, Mark J.; Kuca, Michal; Aragon, Mona L.

    2016-02-02

    A security system includes a structure having a structural surface. The structure is sized to contain an asset therein and configured to provide a forceful breaching delay. The structure has an opening formed therein to permit predetermined access to the asset contained within the structure. The structure includes intrusion detection features within or associated with the structure that are activated in response to at least a partial breach of the structure.

  7. Blackboard Systems.

    DTIC Science & Technology

    1986-06-01

    article stated that although the importance of context, syntax, semantics, and phonological rules in the recognition of speech was accepted, no system had...of, from the lowest to the highest level: parametric, segmental, phonetic , phonemic, syllabic, lexical, phrasal, and conceptual levels (see Figure 3...from classification (classifying acoustic segments into phonetic classes), to recognition (recognizing words) to generation and 42SCe (25] for a

  8. Tychonic System

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    The world system proposed in 1583 by the Danish astronomer Tycho Brahe (1546-1601). Unable to accept the Copernican doctrine that the Earth moves around the Sun, he put forward the view, later disproved by Kepler (1571-1630), that the planets move around the Sun, but the Sun and Moon move around the Earth. The theory explained the observed variations of the phases of Venus, for which the Ptolemai...

  9. Imaging System

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The 1100C Virtual Window is based on technology developed under NASA Small Business Innovation (SBIR) contracts to Ames Research Center. For example, under one contract Dimension Technologies, Inc. developed a large autostereoscopic display for scientific visualization applications. The Virtual Window employs an innovative illumination system to deliver the depth and color of true 3D imaging. Its applications include surgery and Magnetic Resonance Imaging scans, viewing for teleoperated robots, training, and in aviation cockpit displays.

  10. CONTROL SYSTEM

    DOEpatents

    Shannon, R.H.; Williamson, H.E.

    1962-10-30

    A boiling water type nuclear reactor power system having improved means of control is described. These means include provisions for either heating the coolant-moderator prior to entry into the reactor or shunting the coolantmoderator around the heating means in response to the demand from the heat engine. These provisions are in addition to means for withdrawing the control rods from the reactor. (AEC)

  11. Braking system

    DOEpatents

    Norgren, D.U.

    1982-09-23

    A balanced braking system comprising a plurality of braking assemblies located about a member to be braked. Each of the braking assemblies consists of a spring biased piston of a first material fitted into a body of a different material which has a greater contraction upon cooling than the piston material. The piston is provided with a recessed head portion over which is positioned a diaphragm and forming a space therebetween to which is connected a pressurized fluid supply. The diaphragm is controlled by the fluid in the space to contact or withdraw from the member to be braked. A cooling means causes the body within which the piston is fitted to contract more than the piston, producing a tight shrink fit therebetween. The braking system is particularly applicable for selectively braking an arbor of an electron microscope which immobilizes, for example, a vertically adjustable low temperature specimen holder during observation. The system provides balanced braking forces which can be easily removed and re-established with minimal disturbance to arbor location.

  12. Bioregenerative system

    NASA Technical Reports Server (NTRS)

    1987-01-01

    The design course is an eight semester credit multi-disciplinary engineering design course taught primarily to Engineering Science, Aerospace, Electrical and Mechanical Engineering seniors. This year the course project involved the design of the three interrelated loops: atmospheric, liquid nutrient and solid waste management, associated with growing higher plants to support man during long-term space missions. The project is complementary to the NASA Kennedy Space Center Controlled Environmental Life Support System (CELSS) project. The first semester the class worked on a preliminary design for a complete system. This effort included means for monitoring and control of composition, temperature, flow rate, etc., for the atmosphere and liquid nutrient solution; disease and contaminant monitoring and control; plant mechanical support, propagation and harvesting; solid and liquid waste recycling; and system maintenance and refurbishing. The project has significant biological, mechanical, electrical and Al/Robotics aspects. The second semester a small number of subsystems or components, identified as important and interesting during the first semester, were selected for detail design, fabrication, and testing. The class was supported by close cooperation with The Kennedy Space Center and by two teaching assistants. The availability of a dedicated, well equipped project room greatly enhanced the communication and team spirit of the class.

  13. Systemic sclerosis.

    PubMed

    Allanore, Yannick; Simms, Robert; Distler, Oliver; Trojanowska, Maria; Pope, Janet; Denton, Christopher P; Varga, John

    2015-04-23

    Systemic sclerosis is a complex autoimmune disease characterized by a chronic and frequently progressive course and by extensive patient-to-patient variability. Like other autoimmune diseases, systemic sclerosis occurs more frequently in women, with a peak of onset in the fifth decade of life. The exact cause of systemic sclerosis remains elusive but is likely to involve environmental factors in a genetically primed individual. Pathogenesis is dominated by vascular changes; evidence of autoimmunity with distinct autoantibodies and activation of both innate and adaptive immunity; and fibrosis of the skin and visceral organs that results in irreversible scarring and organ failure. Intractable progression of vascular and fibrotic organ damage accounts for the chronic morbidity and high mortality. Early and accurate diagnosis and classification might improve patient outcomes. Screening strategies facilitate timely recognition of life-threatening complications and initiation of targeted therapies to halt their progression. Effective treatments of organ-based complications are now within reach. Discovery of biomarkers - including autoantibodies that identify patient subsets at high risk for particular disease complications or rapid progression - is a research priority. Understanding the key pathogenetic pathways, cell types and mediators underlying disease manifestations opens the door for the development of targeted therapies with true disease-modifying potential. For an illustrated summary of this Primer, visit: http://go.nature.com/lchkcA.

  14. Bioregenerative system

    NASA Technical Reports Server (NTRS)

    1987-01-01

    The design course is an eight semester credit multi-disciplinary engineering design course taught primarily to Engineering Science, Aerospace, Electrical and Mechanical Engineering seniors. This year the course project involved the design of the three interrelated loops: atmospheric, liquid nutrient and solid waste management, associated with growing higher plants to support man during long-term space missions. The project is complementary to the NASA Kennedy Space Center Controlled Environmental Life Support System (CELSS) project. The first semester the class worked on a preliminary design for a complete system. This effort included means for monitoring and control of composition, temperature, flow rate, etc., for the atmosphere and liquid nutrient solution; disease and contaminant monitoring and control; plant mechanical support, propagation and harvesting; solid and liquid waste recycling; and system maintenance and refurbishing. The project has significant biological, mechanical, electrical and Al/Robotics aspects. The second semester a small number of subsystems or components, identified as important and interesting during the first semester, were selected for detail design, fabrication, and testing. The class was supported by close cooperation with The Kennedy Space Center and by two teaching assistants. The availability of a dedicated, well equipped project room greatly enhanced the communication and team spirit of the class.

  15. Development and Optimization of a Dedicated, Hybrid Dual-Modality SPECT-CmT System for Improved Breast Lesion Diagnosis

    DTIC Science & Technology

    2009-01-01

    the Defrise phantom drawn in PENELOPE . Outer and inner cylinder is 8.2cm and 7.5cm in diameter, respectively. Each of the 5 discs (in between the...simulations using PENELOPE was performed by creating an object similar to the Defrise phantom (Fig. 3) and setting the detector at different tilts. The CmT... crossing map of the level set is then used to match gradients in the SPECT image to the level set by using a data structure containing the signed distance

  16. Tunable edge-mode-based mid-infrared plasmonically induced transparency in the coupling system of coplanar graphene ribbons

    NASA Astrophysics Data System (ADS)

    Li, Hong-Ju; Wang, Ling-Ling; Zhang, Bing-Hua; Zhai, Xiang

    2016-01-01

    The graphene ribbon waveguide with two short parallel, coupled coplanar strips is investigated. Because of the extreme destructive interference of the short strip resonators, an outstanding plasmonically induced transparency (PIT) window with a group time delay up to 0.28 ps is achieved in the mid-infrared region, with an excellent ultraslow-light feature. The PIT window is controlled by varying the coupling distance between resonators and is tuned dynamically by a small change in the chemical potential. Numerical results are confirmed using the coupled-mode theory (CMT). The planar structure will benefit the fabrication of plasmonic circuits for slow light and optical switching.

  17. Purification system

    NASA Technical Reports Server (NTRS)

    Flanagan, David T. (Inventor); Gibbons, Randall E. (Inventor)

    1992-01-01

    A system for prolonging the life of a granulated activated charcoal (GAC) water treatment device is disclosed in which an ultraviolet light transparent material is used to constrain water to flow over carbon surfaces. It is configured to receive maximum flux from a UV radiation source for the purpose of preventing microbial proliferation on the carbon surfaces; oxidizing organic contaminants adsorbed from the water onto the carbon surfaces and from biodegradation of adsorbed microbial forms; disinfecting water; and oxidizing organic contaminants in the water.

  18. Bearing system

    DOEpatents

    Kapich, Davorin D.

    1987-01-01

    A bearing system includes backup bearings for supporting a rotating shaft upon failure of primary bearings. In the preferred embodiment, the backup bearings are rolling element bearings having their rolling elements disposed out of contact with their associated respective inner races during normal functioning of the primary bearings. Displacement detection sensors are provided for detecting displacement of the shaft upon failure of the primary bearings. Upon detection of the failure of the primary bearings, the rolling elements and inner races of the backup bearings are brought into mutual contact by axial displacement of the shaft.

  19. Balance System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    TherEx Inc.'s AT-1 Computerized Ataxiameter precisely evaluates posture and balance disturbances that commonly accompany neurological and musculoskeletal disorders. Complete system includes two-strain gauged footplates, signal conditioning circuitry, a computer monitor, printer and a stand-alone tiltable balance platform. AT-1 serves as assessment tool, treatment monitor, and rehabilitation training device. It allows clinician to document quantitatively the outcome of treatment and analyze data over time to develop outcome standards for several classifications of patients. It can evaluate specifically the effects of surgery, drug treatment, physical therapy or prosthetic devices.

  20. Sterilization System

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Cox Sterile Products, Inc.'s Rapid Heat Transfer Sterilizer employs a heat exchange process that induces rapid air movement; the air becomes the heat transfer medium, maintaining a uniform temperature of 375 degrees Fahrenheit. It features pushbutton controls for three timing cycles for different instrument loads, a six-minute cycle for standard unpackaged instruments, eight minutes for certain specialized dental/medical instruments and 12 minutes for packaged instruments which can then be stored in a drawer in sterile condition. System will stay at 375 degrees all day. Continuous operation is not expensive because of the sterilizer's very low power requirements.

  1. Relaxation System

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Environ Corporation's relaxation system is built around a body lounge, a kind of super easy chair that incorporates sensory devices. Computer controlled enclosure provides filtered ionized air to create a feeling of invigoration, enhanced by mood changing aromas. Occupant is also surrounded by multidimensional audio and the lighting is programmed to change colors, patterns, and intensity periodically. These and other sensory stimulators are designed to provide an environment in which the learning process is stimulated, because research has proven that while an individual is in a deep state of relaxation, the mind is more receptive to new information.

  2. Control and dynamic systems

    SciTech Connect

    Leondes, C.T. . Dept. of Electrical Engineering)

    1991-01-01

    This volume covers topics pertaining to analysis and control system techniques for electric power systems. Topics include: computer relaying in power systems, power system generation expansion, expert systems for power systems, and power flow algorithms.

  3. Systems Pharmacology

    PubMed Central

    Boran, Aislyn D. W.; Iyengar, Ravi

    2011-01-01

    We examine how physiology and pathophysiology are studied from a systems perspective, using high-throughput experiments and computational analysis of regulatory networks. We describe the integration of these analyses with pharmacology, which leads to new understanding of drug action and enables drug discovery for complex diseases. Network studies of drug-target relationships can serve as an indication on the general trends in the approved drugs and the drug-discovery progress. There is a growing number of targeted therapies approved and in the pipeline, which meets a new set of problems with efficacy and adverse effects. The pitfalls of these mechanistically based drugs are described, along with how a systems view of drug action is increasingly important to uncover intricate signaling mechanisms that play an important part in drug action, resistance mechanisms, and off-target effects. Computational methodologies enable the classification of drugs according to their structures and to which proteins they bind. Recent studies have combined the structural analyses with analysis of regulatory networks to make predictions about the therapeutic effects of drugs for complex diseases and possible off-target effects. PMID:20687178

  4. Crystal structure of the extracellular domain of human myelin protein zero

    SciTech Connect

    Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C.

    2012-03-27

    Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125

  5. Expert Systems: What Is an Expert System?

    ERIC Educational Resources Information Center

    Duval, Beverly K.; Main, Linda

    1994-01-01

    Describes expert systems and discusses their use in libraries. Highlights include parts of an expert system; expert system shells; an example of how to build an expert system; a bibliography of 34 sources of information on expert systems in libraries; and a list of 10 expert system shells used in libraries. (Contains five references.) (LRW)

  6. Power systems

    NASA Astrophysics Data System (ADS)

    Kaplan, G.

    1982-01-01

    Significant events in current, prototype, and experimental utility power generating systems in 1981 are reviewed. The acceleration of licensing and the renewal of plans for reprocessing of fuel for nuclear power plants are discussed, including the rise of French reactor-produced electricity to over 40% of the country's electrical output. A 4.5 MW fuel cell neared completion in New York City, while three 2.5 MW NASA-designed windpowered generators began producing power in the state of Washington. Static bar compensators, nonflammable-liquid cooled power transformers, and ZnO surge arrestors were used by utilities for the first time, and the integration of a coal gasifier-combined cycle power plant approached the planning phase. An MHD generator was run for 1000 hours and produced 50-60 kWe, while a 20 MVA superconducting generator was readied for testing.

  7. Pumping system

    SciTech Connect

    Kime, J.A.

    1987-05-19

    This patent describes a gas-oil production system for pumping formation fluid in a well through a tubing string within which a down hole pump connects to a hydraulic stroking device through a rod string providing the pump including a plunger reciprocally driven by the hydraulic stroking device toward an upper terminal position during a plunger upstroke. The rod string normally supports the weight of a column of fluid and toward a lower terminal position at the end of a plunger downstroke during which the weight of the column fluid is normally transferred to the tubing string through fluid within the pump. The method for detecting when the well is pumped off comprises: supplying working fluid to the hydraulic stroking device to raise the hydraulic stroking device and thereby move the plunger from the lower terminal position to the upper terminal position; and removing the working fluid at a controlled rate from the hydraulic stroking device.

  8. Systems toxicology.

    PubMed

    Hartung, Thomas; van Vliet, Erwin; Jaworska, Joanna; Bonilla, Leo; Skinner, Nigel; Thomas, Russell

    2012-01-01

    The need for a more mechanistic understanding of the ways in which chemicals modulate biological pathways is urgent if we are to identify and better assess safety issues relating to a wide range of substances developed by the pharmaceutical, chemical, agri-bio, and cosmetic industries. Omics technologies provide a valuable opportunity to refine existing methods and provide information for so-called integrated testing strategies via the creation of signatures of toxicity. By mapping these signatures to underlying pathways of toxicity, some of which have been identified by toxicologists over the last few decades, and bringing them together with pathway information determined from biochemistry and molecular biology, a "systems toxicology" approach will enable virtual experiments to be conducted that can improve the prediction of hazard and the assessment of compound toxicity.

  9. Transfer system

    DOEpatents

    Kurosawa, Kanji; Koga, Bunichiro; Ito, Hideki; Kiriyama, Shigeru; Higuchi, Shizuo

    2003-05-20

    A transport system includes a traveling rail (1) which constitutes a transport route and a transport body (3) which is capable of traveling on the traveling rail in the longitudinal direction of the traveling rail. Flexible drive tubes (5) are arranged on the traveling rail in the longitudinal direction of the traveling rail. The transport body includes a traveling wheel (4) which is capable of rolling on the traveling rail and drive wheels (2) which are capable of rolling on the drive tubes upon receiving the rotational drive power generated by pressure of a pressure medium supplied to the drive tubes while depressing the drive tubes. The traveling rail includes a plurality of transport sections and the transport body is capable of receiving a rotational drive force from the drive tubes at every transport sections. If necessary, a transport route changeover switch which changes over the transport route can be provided between the transport sections.

  10. Tracking system

    SciTech Connect

    Leroy, V. A.; Gaedtke, H. D.

    1985-10-15

    A system of tracking the sun each day of the year with compensation for changes in time of sunrise and time of sunset as well as sun declination on a day to day basis, declination being under control of a crank that makes one revolution per year. The equation of time is under control of a cam that also revolves once a year and resets the clock to reflect solar rather than mean solar time in order to properly follow the sun. The position of sun acquisition and loss are a function of the declination and the time is a function of the clock corrected via the cam for equation of time. Thus, when the declination is reset each day, it sets the position of acquisition and loss while the clock, now set for the change due to the equation of time, determines the time of acquisition and loss.

  11. Intelligent Engine Systems: Bearing System

    NASA Technical Reports Server (NTRS)

    Singh, Arnant P.

    2008-01-01

    The overall requirements necessary for sensing bearing distress and the related criteria to select a particular rotating sensor were established during the phase I. The current phase II efforts performed studies to evaluate the Robustness and Durability Enhancement of the rotating sensors, and to design, and develop the Built-in Telemetry System concepts for an aircraft engine differential sump. A generic test vehicle that can test the proposed bearing diagnostic system was designed, developed, and built. The Timken Company, who also assisted with testing the GE concept of using rotating sensors for the differential bearing diagnostics during previous phase, was selected as a subcontractor to assist General Electric (GE) for the design, and procurement of the test vehicle. A purchase order was prepared to define the different sub-tasks, and deliverables for this task. The University of Akron was selected to provide the necessary support for installing, and integrating the test vehicle with their newly designed test facility capable of simulating the operating environment for the planned testing. The planned testing with good and damaged bearings will be on hold pending further continuation of this effort during next phase.

  12. Effectiveness of real-time quantitative PCR compare to repeat PCR for the diagnosis of Charcot-Marie-Tooth Type 1A and hereditary neuropathy with liability to pressure palsies.

    PubMed

    Choi, Jong Rak; Lee, Woon Hyoung; Sunwoo, Il Nam; Lee, Eun Kyung; Lee, Chang Hoon; Lim, Jong Baeck

    2005-06-30

    The majority of cases of Charcot-Marie-Tooth type 1A (CMT1A) and of hereditary neuropathy with a liability to pressure palsies (HNPP) are the result of heterozygosity for the duplication or deletion of peripheral myelin protein 22 gene (PMP22) on 17p11.2. Southern blots, pulsed-field gel electrophoresis (PFGE), fluorescence in situ hybridization (FISH) and polymorphic marker analysis are currently used diagnostic methods. But they are time-consuming, labor-intensive and have some significant limitations. We describe a rapid real- time quantitative PCR method for determining gene copy number for the identification of DNA duplication or deletion occurring in CMT1A or HNPP and compare the results obtained with REP-PCR. Six patients with CMT1A and 14 patients with HNPP [confirmed by Repeat (REP)-PCR], and 16 patients with suspicious CMT1A and 13 patients with suspicious HNPP [negative REP-PCR], and 15 normal controls were studied. We performed REP-PCR, which amplified a 3.6 Kb region (including a 1.7Kb recombination hotspot), using specific CMT1A-REP and real-time quantitative PCR on the LightCycler system. Using a comparative threshold cycle (Ct) method and beta -globin as a reference gene, the gene copy number of the PMP22 gene was quantified. The PMP22 duplication ratio ranged from 1.35 to 1.74, and the PMP22 deletion ratio from 0.41 to 0.53. The PMP22 ratio in normal controls ranged from 0.81 to 1.12. All 6 patients with CMT1A and 14 patients with HNPP confirmed by REP-PCR were positive by real-time quantitative PCR. Among the 16 suspicious CMT1A and 13 suspicious HNPP with negative REP-PCR, 2 and 4 samples, respectively, were positive by real-time quantitative PCR. Real-time quantitative PCR is a more sensitive and more accurate method than REP-PCR for the detection of PMP22 duplications or deletions, and it is also faster and easier than currently available methods. Therefore, we believe that the real-time quantitative method is useful for diagnosing CMT1A and

  13. Separation system

    DOEpatents

    Rubin, Leslie S.

    1986-01-01

    A separation system for dewatering radioactive waste materials includes a disposal container, drive structure for receiving the container, and means for releasably attaching the container to the drive structure. Separation structure disposed in the container adjacent the inner surface of the side wall structure retains solids while allowing passage of liquids. Inlet port structure in the container top wall is normally closed by first valve structure that is centrifugally actuated to open the inlet port and discharge port structure at the container periphery receives liquid that passes through the separation structure and is normally closed by second valve structure that is centrifugally actuated to open the discharge ports. The container also includes coupling structure for releasable engagement with the centrifugal drive structure. Centrifugal force produced when the container is driven in rotation by the drive structure opens the valve structures, and radioactive waste material introduced into the container through the open inlet port is dewatered, and the waste is compacted. The ports are automatically closed by the valves when the container drum is not subjected to centrifugal force such that containment effectiveness is enhanced and exposure of personnel to radioactive materials is minimized.

  14. Incinerator system

    SciTech Connect

    Rathmell, R.K.

    1986-10-07

    An incineration system is described which consists of: combustion chamber structure having an inlet, an outlet, and burner structure in the combustion chamber, heat exchanger structure defining a chamber, divider structure between the heat exchanger chamber and the combustion chamber, an array of tubes extending through the heat exchanger chamber to the inlet of the combustion chamber at the divider structure. The heat exchanger chamber has an inlet coupled to the outlet of the combustion chamber for flow of the combustion products discharged from the combustion chamber through the heat exchanger chamber over the tubes in heat exchange relation, and an outlet for discharge of products from the heat exchanger chamber, aspirator sleeve structure secured to the divider structure between the heat exchanger chamber and the combustion chamber. Each aspirator sleeve receives the outlet end of a heat exchanger tube in slip fit relation so that the heat exchanger tubes are free to thermally expand longitudinally within the aspirator sleeves, and means for flowing vapor through the heat exchanger tubes into the combustion chamber at sufficiently high velocity to produce a reduced pressure effect in the aspirator sleeves in the heat exchanger chamber to draw a minor fraction of combustion products through the aspirator sleeves into the combustion chamber for reincineration.

  15. Systemic vasculitis.

    PubMed

    Sharma, Poonam; Sharma, Sanjeev; Baltaro, Richard; Hurley, John

    2011-03-01

    The systemic vasculitides are characterized by inflammation of blood vessel walls. Vessels of any type, in any organ can be affected, resulting in a broad spectrum of signs and symptoms. The heterogenous nature of vasculitides presents a diagnostic challenge. The American College of Rheumatology classification criteria and the Chapel Hill Consensus Conference nomenclature are the most widely used to distinguish different forms of vasculitis. The Chapel Hill Consensus Conference nomenclature defines 10 primary vasculitides based on vessel size (large, medium, and small). The diagnosis relies on the recognition of a compatible clinical presentation supported by specific laboratory or imaging tests and confirmatory histology. Antineutrophilic cytoplasmic antibody testing has been of particular benefit in defining a subgroup of small vessel vasculitides. Treatment is based on clinical presentation and the pattern of organ involvement. Glucocorticoids are the primary treatment for many forms of vasculitis. Additional immunosuppressive agents, including methotrexate and cyclophosphamide, are sometimes required. Newer approaches, such as the use of anti-tumor necrosis factor or B cell therapies, are being tried in resistant cases. Patients can experience considerable treatment-related toxicity, especially infection from immunosuppressive therapy and adverse effects from steroids (e.g., osteoporosis, diabetes mellitus, cataract). Vitamin D and calcium prophylaxis are recommended in patients on long-term steroid therapy.

  16. New Systems Produced by Systemic Change

    ERIC Educational Resources Information Center

    Battino, Wendy; Clem, Jo; Caine, Renate N.; Reigeluth, Charles M.; Chapman, Carrie; Flinders, David J.; Malopinsky, Larissa V.

    2006-01-01

    This article presents new systems produced by systemic change. First is Systemic Changes in the Chugach School District by Wendy Battino and Jo Clem. Second is Systemic Changes in Public Schools through Brain-Based Learning by Renate N. Caine. Third is A Vision of an Information-Age Educational System by Charles M. Reigeluth. Fourth is Systemic…

  17. New Systems Produced by Systemic Change

    ERIC Educational Resources Information Center

    Battino, Wendy; Clem, Jo; Caine, Renate N.; Reigeluth, Charles M.; Chapman, Carrie; Flinders, David J.; Malopinsky, Larissa V.

    2006-01-01

    This article presents new systems produced by systemic change. First is Systemic Changes in the Chugach School District by Wendy Battino and Jo Clem. Second is Systemic Changes in Public Schools through Brain-Based Learning by Renate N. Caine. Third is A Vision of an Information-Age Educational System by Charles M. Reigeluth. Fourth is Systemic…

  18. Airborne Global Positioning System Antenna System

    DTIC Science & Technology

    2004-10-14

    GLOBAL POSITIONING SYSTEM ANTENNA SYSTEM DISTRIBUTION: SMC/ GP (3 cys); AFFSA...standard that airborne Global Positioning System ( GPS ) antenna system must meet to be identified with the applicable MSO marking. The similarity of...UNCLASSIFIED DOCUMENT NO. DATE NO. MSO-C144 14 Oct 04 Initial Release REV: REV: SHEET 1 OF 16 TITLE: AIRBORNE GLOBAL POSITIONING SYSTEM

  19. Integration and Enhancement of the Saber Wargame

    DTIC Science & Technology

    1993-12-01

    34dentification to be saved by the component. 77 ACTIVATE Figure 36. State Diagram for Work-Button Object I Modif cmt CREATE BI IDLE MDF Figure 37...cases this can cause images to appear warped when shown on various systems. The solution is to use a unit of length rather than the pixel. Saber uses the

  20. Endocrine System (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Endocrine System KidsHealth > For Teens > Endocrine System A A A ... is called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  1. System safety education focused on system management

    NASA Technical Reports Server (NTRS)

    Grose, V. L.

    1971-01-01

    System safety is defined and characteristics of the system are outlined. Some of the principle characteristics include role of humans in hazard analysis, clear language for input and output, system interdependence, self containment, and parallel analysis of elements.

  2. Kinetic stability analysis of protein assembly on the center manifold around the critical point.

    PubMed

    Tsuruyama, Tatsuaki

    2017-02-02

    Non-linear kinetic analysis is a useful method for illustration of the dynamic behavior of cellular biological systems. To date, center manifold theory (CMT) has not been sufficiently applied for stability analysis of biological systems. The aim of this study is to demonstrate the application of CMT to kinetic analysis of protein assembly and disassembly, and to propose a novel framework for nonlinear multi-parametric analysis. We propose a protein assembly model with nonlinear kinetics provided by the fluctuation in monomer concentrations during their diffusion. When the diffusion process of a monomer is self-limited to give kinetics non-linearity, numerical simulations suggest the probability that the assembly and disassembly oscillate near the critical point. We applied CMT to kinetic analysis of the center manifold around the critical point in detail, and successfully demonstrated bifurcation around the critical point, which explained the observed oscillation. The stability kinetics of the present model based on CMT illustrates a unique feature of protein assembly, namely non-linear behavior. Our findings are expected to provide methodology for analysis of biological systems.

  3. Expanding Alternative Delivery Systems.

    ERIC Educational Resources Information Center

    Baltzer, Jan A.

    Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

  4. RADAR WARNING SYSTEM,

    DTIC Science & Technology

    RADAR TRACKING, *AIRCRAFT DEFENSE SYSTEMS, RADAR EQUIPMENT, AIR TO AIR, SEARCH RADAR, GUIDED MISSILES, HIGH SPEED BOMBING, EARLY WARNING SYSTEMS, FIRE CONTROL SYSTEM COMPONENTS, AIRCRAFT, TIME, CHINA.

  5. System design description cone penetrometer system

    SciTech Connect

    Seda, R.Y., Westinghouse Hanford

    1996-08-12

    The system design description documents in detail the design of the cone penetrometer system. The systems includes the cone penetrometer physical package, raman spectroscopy package and moisture sensor package. Information pertinent to the system design, development, fabrication and testing is provided.

  6. Networked control of microgrid system of systems

    NASA Astrophysics Data System (ADS)

    Mahmoud, Magdi S.; Rahman, Mohamed Saif Ur; AL-Sunni, Fouad M.

    2016-08-01

    The microgrid has made its mark in distributed generation and has attracted widespread research. However, microgrid is a complex system which needs to be viewed from an intelligent system of systems perspective. In this paper, a network control system of systems is designed for the islanded microgrid system consisting of three distributed generation units as three subsystems supplying a load. The controller stabilises the microgrid system in the presence of communication infractions such as packet dropouts and delays. Simulation results are included to elucidate the effectiveness of the proposed control strategy.

  7. From systems biology to systems biomedicine.

    PubMed

    Antony, Paul M A; Balling, Rudi; Vlassis, Nikos

    2012-08-01

    Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine.

  8. D0 Cryo System Control System Autodialer

    SciTech Connect

    Urbin, J.; /Fermilab

    1990-04-17

    The DO cryogenic system is controlled by a TI565-PLC based control system. This allows the system to be unmanned when in steady state operation. System experts will need to be contacted when system parameters exceed normal operating points and reach alarm setpoints. The labwide FIRUS system provides one alarm monitor and communication link. An autodialer provides a second and more flexible alarm monitor and communication link. The autodialer monitors contact points in the control system and after receiving indication of an alarm accesses a list of experts which it calls until it receives an acknowledgement. There are several manufacturers and distributors of autodialer systems. This EN explains the search process the DO cryo group used to fmd an autodialer system that fit the cryo system's needs and includes information and specs for the unit we chose.

  9. Mass storage system reference model system management

    SciTech Connect

    Collins, B.; McLarty, T.

    1988-01-01

    System Management is the collection of functions that are primarily concerned with the control, performance and utilization of the Mass Storage System defined by the Mass Storage System Reference Model. These functions are often very site-dependent, involve human decision making, and span multiple ''severs'' of the Mass Storage System. The functions may be implemented as standalone programs, may be integrated with the other Mass Storage System software, or may just be policy. 4 refs.

  10. Global Positioning System Shipborne Reference System

    DTIC Science & Technology

    1997-09-30

    Office of Naval Research Space and Remote Sensing 1997 Annual Report 1 GLOBAL POSITIONING SYSTEM SHIPBORNE REFERENCE SYSTEM James R. Clynch...N00014-97-WR30044 LONG-TERM GOAL The long term goal is to improve the navigation capability of naval vessels using the Global Positioning System ...COVERED 00-00-1997 to 00-00-1997 4. TITLE AND SUBTITLE Global Positioning System Shipborne Reference System 5a. CONTRACT NUMBER 5b. GRANT

  11. Control and dynamic systems

    SciTech Connect

    Leondes, C.T. . Dept. of Electrical Engineering)

    1991-01-01

    This volume contains papers on analysis and control system techniques for electric power systems. Topics include: modeling and control of electric power systems, dynamic state estimation techniques, optimal power flow algorithms, and neural networks in power systems.

  12. Endocrine System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Endocrine System KidsHealth > For Parents > Endocrine System A A A ... to help the body function properly. About the Endocrine System The foundations of the endocrine system are the ...

  13. Immune System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Immune System KidsHealth > For Parents > Immune System A A A ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ...

  14. Quantify information system benefits

    SciTech Connect

    Koppel, L.B.

    1995-06-01

    What are information systems and how do they relate to control systems? How do information systems produce benefits in hydrocarbon processing? What are some examples of benefit-generating information system applications? Information System Benefits (ISBEN) is a structured methodology for estimating information system benefits in hydrocarbon processing. The paper discusses information and control systems, information system benefits and applications, objectives, strategies and measures of ISBEN, ISBEN business drivers, ISBEN database, ISBEN methodology, and implementation.

  15. Control and dynamic systems

    SciTech Connect

    Leondes, C.T. . Dept. of Electrical Engineering)

    1991-01-01

    This book covers analysis and control system techniques for electric power systems. Topics include: concurrent processing in power system analysis, power system protection, voltage collapse, reliability techniques in large electric power systems, optimization in hydroelectric systems, and linear programming methods for optimal energy plant operation.

  16. Practical systems thinking

    NASA Astrophysics Data System (ADS)

    Konkarikoski, K.; Ritala, R.; Ihalainen, H.

    2010-07-01

    System is a dynamic and complex whole, interacting as a structured functional unit. Systems thinking provides tools for understanding a such system structure and its dynamic behavior. Practical systems thinking course teaches first year bachelor students basics about systems and how open problem can be formulated to system task.

  17. System of systems modeling and analysis.

    SciTech Connect

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E.; Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  18. System Software Framework for System of Systems Avionics

    NASA Technical Reports Server (NTRS)

    Ferguson, Roscoe C.; Peterson, Benjamin L; Thompson, Hiram C.

    2005-01-01

    Project Constellation implements NASA's vision for space exploration to expand human presence in our solar system. The engineering focus of this project is developing a system of systems architecture. This architecture allows for the incremental development of the overall program. Systems can be built and connected in a "Lego style" manner to generate configurations supporting various mission objectives. The development of the avionics or control systems of such a massive project will result in concurrent engineering. Also, each system will have software and the need to communicate with other (possibly heterogeneous) systems. Fortunately, this design problem has already been solved during the creation and evolution of systems such as the Internet and the Department of Defense's successful effort to standardize distributed simulation (now IEEE 1516). The solution relies on the use of a standard layered software framework and a communication protocol. A standard framework and communication protocol is suggested for the development and maintenance of Project Constellation systems. The ARINC 653 standard is a great start for such a common software framework. This paper proposes a common system software framework that uses the Real Time Publish/Subscribe protocol for framework-to-framework communication to extend ARINC 653. It is highly recommended that such a framework be established before development. This is important for the success of concurrent engineering. The framework provides an infrastructure for general system services and is designed for flexibility to support a spiral development effort.

  19. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry, Jr.

    1991-01-01

    Significant advances have occurred during the last decade in intelligent systems technologies (a.k.a. knowledge-based systems, KBS) including research, feasibility demonstrations, and technology implementations in operational environments. Evaluation and simulation data obtained to date in real-time operational environments suggest that cost-effective utilization of intelligent systems technologies can be realized for Automated Rendezvous and Capture applications. The successful implementation of these technologies involve a complex system infrastructure integrating the requirements of transportation, vehicle checkout and health management, and communication systems without compromise to systems reliability and performance. The resources that must be invoked to accomplish these tasks include remote ground operations and control, built-in system fault management and control, and intelligent robotics. To ensure long-term evolution and integration of new validated technologies over the lifetime of the vehicle, system interfaces must also be addressed and integrated into the overall system interface requirements. An approach for defining and evaluating the system infrastructures including the testbed currently being used to support the on-going evaluations for the evolutionary Space Station Freedom Data Management System is presented and discussed. Intelligent system technologies discussed include artificial intelligence (real-time replanning and scheduling), high performance computational elements (parallel processors, photonic processors, and neural networks), real-time fault management and control, and system software development tools for rapid prototyping capabilities.

  20. Systems engineering and analysis

    SciTech Connect

    Blanchard, B.S.; Fabrycky, W.J.

    1981-01-01

    An introduction to systems is provided and tools for systems analysis are considered, taking into account system definitions and concepts, approaches for bringing systems into being, models in systems analysis, economic analysis techniques, mathematical modeling and optimization, probability and statistics, queuing theory and analysis, and control concepts and techniques. The system design process is discussed along with the design for operational feasibility, systems engineering management, and system design case studies. Attention is given to conceptual design, preliminary system design, detail design and development, system test and evaluation, design for reliability, design for maintainability, design for supportability, design for economic feasibility, communication system design, finite population system design, energy storage system design, and procurement-inventory system design.

  1. [X-33 Systems

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Lockheed Martin Skunk Works has compiled an Annual Performance Report of the X-33/RLV Program. This report consists of individual reports from all industry team members, as well as NASA team centers. This portion of the report is comprised of a status report of Allied-Signal Aerospace's contribution to the program. The following is a summary of the work reviewed under their portion of the agreement: (1) Communication Systems; (2) Environmental Control Systems- Active Thermal Control System (ATCS), Purge and Vent System, Hydrogen Detection System (HDS), Avionics Bay Inerting System (ABIS), and Flush Air Data System (FADS); (2) Landing Systems; (3) Power Management and Generation Systems; (4) Flight Control Actuation System (FCAS)- Electric Power Control & Distribution System (EPCDS), and Battery Power System (BPS); and (5) Vehicle Management Systems (VMS)- VMS Hardware, VMS Software Development Activities, and System Integration Laboratory (SIL).

  2. Freedom System Text and Graphics System (TAGS)

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The Text and Graphics System (TAGS) is a high-resolution facsimile system that scans text or graphics material and converts the analog SCAN data into serial digital data. This video shows the TAGS in operation.

  3. Language as a System of Systems

    ERIC Educational Resources Information Center

    Mulder, J. W. F.; Hervey, S. G. J.

    1975-01-01

    Based on Mulder's previous classification of all semiotic systems designed to describe the system of discrete features in human languages, this article explores a further subclassification of the genus language into species. (CLK)

  4. Language as a System of Systems

    ERIC Educational Resources Information Center

    Mulder, J. W. F.; Hervey, S. G. J.

    1975-01-01

    Based on Mulder's previous classification of all semiotic systems designed to describe the system of discrete features in human languages, this article explores a further subclassification of the genus language into species. (CLK)

  5. LCLS XTOD Attenuator System System Concept Report

    SciTech Connect

    Kishiyama, K; Roeben, M; Trent, J; Ryutov, D; Shen, S

    2006-04-12

    The attenuator system for the Linac Coherent Light Source (LCLS) X-ray Transport, Optics and Diagnostics (XTOD) system has been configured and analyzed by the Lawrence Livermore National Laboratory's New Technologies Engineering Division (NTED) as requested by the SLAC/LCLS program. The system layout, performance analyses and selection of the vacuum components are presented in this System Conceptual Review (SCR) report. Also included are the plans for prototype, procurement, mechanical integration, and the cost estimates.

  6. A clinical study to evaluate the efficacy of intravitreal Anti-VEGF therapy in treating macular edema due to retinal venous occlusions

    PubMed Central

    Kumar, Poninder; Banarji, Ajay; Patyal, Sagarika; Gurunadh, V.S.; Ahluwalia, T.S.; Oli, Avadesh; Moulick, P.S.; Makker, Anuradha

    2013-01-01

    Background A non-randomized, interventional study was carried out various types of retinal venous occlusions with significant macular edema who required an Anti-VEGF injection. Method One hundred and one consecutive patients diagnosed as a case of CRVO/HCRVO/BRVO were enrolled in the study provided they had significant macular edema. Atleast three intra-vitreal injections of Anti-VEGFs were given and both the pre and post injections BCVA and CMT on OCT were observed and analyzed. Results 87 patients (86.14%) showed a significant improvement of vision of atleast two lines on the Snellen's and mean BCVA improved from log MAR +1.084 to log MAR +0.455. CMT on OCT showed reduction in thickness after Anti-VEGF therapy in 99 patients out of 101 and mean CMT decreased from 586.30 μ at baseline to 329.50 μ. Both of these findings were statistically very significant. Conclusions Anti-VEGF therapy had a marked improvement in BCVA along with a dramatic reduction in CMT in the vast majority of RVOs patients with no serious ocular or systemic side effects. PMID:24600120

  7. Evaluation of synchrotron X-ray computerized microtomography for the visualization of transport processes in low-porosity materials.

    PubMed

    Altman, Susan J; Peplinski, William J; Rivers, Mark L

    2005-07-01

    Synchrotron-source X-ray computerized microtomography (CMT) is evaluated as a method to visualize transport processes. We conclude that CMT is adequate for visualization of transport experiments if the right conditions exist. Namely, 1) not much more than one-order-of-magnitude range in concentration data is needed for the study, 2) the pore space in the samples are greater than approximately 2--50 mum, depending on the sample size and system setup; 3) the sample is fine-grained enough so that a representative elemental volume (REV) can be contained by a 2--10 mm diameter sample, and 4) the transport process is slow enough that significant changes do not occur within the 25--50 min (and possibly less in the future) needed to collect data for one three-dimensional image. Absorption edge difference imaging (AEDI) in association with CMT is introduced as a method to enhance pore-space visualization. We successfully imaged the pore space in a low-porosity granodiorite, diorite and fine-grained granite cores and a higher-porosity soil aggregate sample. We found that the pore space important to transport in the core samples was smaller than what we were able to visualize with CMT. We also made rudimentary associations of minerals with pore-space location.

  8. Charcot–Marie–Tooth disease and intracellular traffic

    PubMed Central

    Bucci, Cecilia; Bakke, Oddmund; Progida, Cinzia

    2012-01-01

    Mutations of genes whose primary function is the regulation of membrane traffic are increasingly being identified as the underlying causes of various important human disorders. Intriguingly, mutations in ubiquitously expressed membrane traffic genes often lead to cell type- or organ-specific disorders. This is particularly true for neuronal diseases, identifying the nervous system as the most sensitive tissue to alterations of membrane traffic. Charcot–Marie–Tooth (CMT) disease is one of the most common inherited peripheral neuropathies. It is also known as hereditary motor and sensory neuropathy (HMSN), which comprises a group of disorders specifically affecting peripheral nerves. This peripheral neuropathy, highly heterogeneous both clinically and genetically, is characterized by a slowly progressive degeneration of the muscle of the foot, lower leg, hand and forearm, accompanied by sensory loss in the toes, fingers and limbs. More than 30 genes have been identified as targets of mutations that cause CMT neuropathy. A number of these genes encode proteins directly or indirectly involved in the regulation of intracellular traffic. Indeed, the list of genes linked to CMT disease includes genes important for vesicle formation, phosphoinositide metabolism, lysosomal degradation, mitochondrial fission and fusion, and also genes encoding endosomal and cytoskeletal proteins. This review focuses on the link between intracellular transport and CMT disease, highlighting the molecular mechanisms that underlie the different forms of this peripheral neuropathy and discussing the pathophysiological impact of membrane transport genetic defects as well as possible future ways to counteract these defects. PMID:22465036

  9. Remodelling of motor nerve terminals in demyelinating axons of periaxin null mutant mice

    PubMed Central

    Court, Felipe A; Brophy, Peter J; Ribchester, Richard R

    2015-01-01

    Myelin formation around axons increases nerve conduction velocity and regulates phenotypic characteristics of the myelinated axon. In the peripheral nervous system, demyelinating forms of hereditary Charcot-Marie-Tooth (CMT) diseases, due to Schwann-cell intrinsic molecular defects, leads to reduced nerve conduction velocity and changes in the axonal phenotype. Several mouse models of CMT diseases have been generated, allowing the study of consequences of demyelination in peripheral nerve fibres. Nevertheless, the effect of demyelination at the level of the neuromuscular synapse has been largely overlooked. Here we show that in the periaxin knock-out mice, a model of CMT condition, neuromuscular junctions develop profound morphological changes in pre-terminal region of motoraxons. These changes include extensive preterminal branches which originate in demyelinated regions of the nerve fibre and axonal swellings associated with residually-myelinated regions of the fibre. Using intracellular recording from muscle fibres we detected asynchronous failure of action potential transmission at high but not low stimulation frequencies, a phenomenon consistent with branch point failure. Taken together, our morphological and electrophysiological findings suggest that preterminal branching due to segmental demyelination near the neuromuscular synapse in periaxin KO mice may underlie phenotypic disabilities present in this mouse model of CMT disease. These results opens a new avenue of research in order to understand the cellular changes responsible for clinical disabilities in demyelinating conditions. PMID:18205176

  10. Shaker-Related Potassium Channels in the Central Medial Nucleus of the Thalamus Are Important Molecular Targets for Arousal Suppression by Volatile General Anesthetics

    PubMed Central

    Birch, Alexandra M.; Tanaka, Brian S.; Sokolov, Yuri; Goldin, Alan L.; Chandy, K. George; Hall, James E.; Alkire, Michael T.

    2013-01-01

    The molecular targets and neural circuits that underlie general anesthesia are not fully elucidated. Here, we directly demonstrate that Kv1-family (Shaker-related) delayed rectifier K+ channels in the central medial thalamic nucleus (CMT) are important targets for volatile anesthetics. The modulation of Kv1 channels by volatiles is network specific as microinfusion of ShK, a potent inhibitor of Kv1.1, Kv1.3, and Kv1.6 channels, into the CMT awakened sevoflurane-anesthetized rodents. In heterologous expression systems, sevoflurane, isoflurane, and desflurane at subsurgical concentrations potentiated delayed rectifier Kv1 channels at low depolarizing potentials. In mouse thalamic brain slices, sevoflurane inhibited firing frequency and delayed the onset of action potentials in CMT neurons, and ShK-186, a Kv1.3-selective inhibitor, prevented these effects. Our findings demonstrate the exquisite sensitivity of delayed rectifier Kv1 channels to modulation by volatile anesthetics and highlight an arousal suppressing role of Kv1 channels in CMT neurons during the process of anesthesia. PMID:24107962

  11. Inflammation-related microRNA expression level in the bovine milk is affected by mastitis

    PubMed Central

    Lai, Yu-Chang; Fujikawa, Takuro; Maemura, Tadashi; Ando, Takaaki; Kitahara, Go; Endo, Yasuyuki; Yamato, Osamu; Koiwa, Masateru; Kubota, Chikara

    2017-01-01

    MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155, miR-222, and miR-383 was significantly upregulated in California mastitis test positive (CMT+) milk. We further analyzed these miRNA using a chip-based QuantStudio Digital PCR System. The digital PCR results correlated with those of qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR-383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+ milk. These miRNA exhibited sensitivity and specificity greater than 80% for differentiating between CMT+ milk and normal milk. Our findings suggest that inflammation-related miRNA expression level in the bovine milk was affected by mastitis, and miRNA in milk have potential for use as biomarkers of bovine mastitis. PMID:28520748

  12. Inflammation-related microRNA expression level in the bovine milk is affected by mastitis.

    PubMed

    Lai, Yu-Chang; Fujikawa, Takuro; Maemura, Tadashi; Ando, Takaaki; Kitahara, Go; Endo, Yasuyuki; Yamato, Osamu; Koiwa, Masateru; Kubota, Chikara; Miura, Naoki

    2017-01-01

    MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155, miR-222, and miR-383 was significantly upregulated in California mastitis test positive (CMT+) milk. We further analyzed these miRNA using a chip-based QuantStudio Digital PCR System. The digital PCR results correlated with those of qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR-383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+ milk. These miRNA exhibited sensitivity and specificity greater than 80% for differentiating between CMT+ milk and normal milk. Our findings suggest that inflammation-related miRNA expression level in the bovine milk was affected by mastitis, and miRNA in milk have potential for use as biomarkers of bovine mastitis.

  13. DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

    PubMed

    Hong, Young Bin; Kang, Junghee; Kim, Ji Hyun; Lee, Jinho; Kwak, Geon; Hyun, Young Se; Nam, Soo Hyun; Hong, Hyun Dae; Choi, Yu-Ri; Jung, Sung-Chul; Koo, Heasoo; Lee, Ji Eun; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies.

  14. Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease.

    PubMed

    Shen, Sida; Benoy, Veronick; Bergman, Joel A; Kalin, Jay H; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P

    2016-02-17

    Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacological treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacological therapy. Therefore, we aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochemical properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, we developed several analogues that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound 23d that possesses improved biochemical, functional, and druglike properties compared to tubastatin A.

  15. Uncertainties related to the representation of momentum transport in shallow convection

    NASA Astrophysics Data System (ADS)

    Schlemmer, Linda; Bechtold, Peter; Sandu, Irina; Ahlgrimm, Maike

    2017-04-01

    The vertical transport of horizontal momentum by convection has an important impact on the general circulation of the atmosphere as well as on the life cycle and track of cyclones. So far convective momentum transport (CMT) has mostly been studied for deep convection, whereas little is known about its characteristics and importance in shallow convection. In this study CMT by shallow convection is investigated by analyzing both data from large-eddy simulations (LES) and simulations performed with the Integrated Forecasting System (IFS) of the European Centre for Medium-Range Weather Forecasts (ECMWF). In addition, the central terms underlying the bulk mass-flux parametrization of CMT are evaluated offline. Further, the uncertainties related to the representation of CMT are explored by running the stochastically perturbed parametrizations (SPP) approach of the IFS. The analyzed cases exhibit shallow convective clouds developing within considerable low-level wind shear. Analysis of the momentum fluxes in the LES data reveals significant momentum transport by the convection in both cases, which is directed down-gradient despite substantial organization of the cloud field. A detailed inspection of the convection parametrization reveals a very good representation of the entrainment and detrainment rates and an appropriate representation of the convective mass and momentum fluxes. To determine the correct values of mass-flux and in-cloud momentum at the cloud base in the parametrization yet remains challenging. The spread in convection-related quantities generated by the SPP is reasonable and addresses many of the identified uncertainties.

  16. Uncertainties related to the representation of momentum transport in shallow convection

    NASA Astrophysics Data System (ADS)

    Schlemmer, L.; Bechtold, P.; Sandu, I.; Ahlgrimm, M.

    2017-06-01

    Convective momentum transport (CMT) has mostly been studied for deep convection, whereas little is known about its characteristics and importance in shallow convection. In this study, CMT by shallow convection is investigated by analyzing both data from large-eddy simulations (LESs) and reforecasts performed with the Integrated Forecasting System (IFS) of the European Centre for Medium-Range Weather Forecasts (ECMWF). In addition, the central terms underlying the bulk mass-flux parametrization of CMT are evaluated offline. Further, the uncertainties related to the representation of CMT are explored by running the stochastically perturbed parametrizations (SPP) approach of the IFS. The analyzed cases exhibit shallow convective clouds developing within considerable low-level wind shear. Analysis of the momentum fluxes in the LES data reveals significant momentum transport by the convection in both cases, which is directed downgradient despite substantial organization of the cloud field. A detailed inspection of the convection parametrization reveals a very good representation of the entrainment and detrainment rates and an appropriate representation of the convective mass and momentum fluxes. To determine the correct values of mass-flux and in-cloud momentum at the cloud base in the parametrization yet remains challenging. The spread in convection-related quantities generated by the SPP is reasonable and addresses many of the identified uncertainties.

  17. A novel GJB1 frameshift mutation produces a transient CNS symptom of X-linked Charcot-Marie-Tooth disease.

    PubMed

    Sakaguchi, Hideya; Yamashita, Satoshi; Miura, Akiko; Hirahara, Tomoo; Kimura, En; Maeda, Yasushi; Terasaki, Tadashi; Hirano, Teruyuki; Uchino, Makoto

    2011-02-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common variant of CMT and is caused by mutations in the GJB1 gene encoding connexin 32. Some CMT1X patients with GJB1 missense mutations have shown transient central nervous system (CNS) symptoms with abnormal brain magnetic resonance imaging (MRI). Herein we report the first case with a novel GJB1 frameshift mutation that associates with a transient CNS symptom. The patient noticed high-arched feet and limited ankle dorsiflexion in early childhood; he transiently developed numbness and paresis of left face and arm, and dysphagia, with abnormal brain MRI. Although the CNS symptoms recovered within several hours without treatment, intravenous immunoglobulin (IVIg) therapy ameliorated progressing symptoms such as those of toe extensor muscles. His mother had been diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), and repetitive IVIg treatments had relieved the symptoms. Therefore, inflammation might be involved in the pathophysiology of CMT1X with the GJB1 mutation, while molecular analysis revealed that the mutant GJB1 was more rapidly degraded by the proteasome pathway known as endoplasmic reticulum (ER)-associated degradation.

  18. General Systems Theory and Instructional Systems Design.

    ERIC Educational Resources Information Center

    Salisbury, David F.

    1990-01-01

    Describes basic concepts in the field of general systems theory (GST) and identifies commonalities that exist between GST and instructional systems design (ISD). Models and diagrams that depict system elements in ISD are presented, and two matrices that show how GST has been used in ISD literature are included. (11 references) (LRW)

  19. Systems Theory, Systems Technology, and Curriculum Design.

    ERIC Educational Resources Information Center

    Pratt, David

    1978-01-01

    John Goodlad (1958) stated that "Nowhere in education is there greater need for a conceptual system to guide decision-making than the field of curriculum." This research attempts to explore ways in which systems thinking can provide a conceptual system, to illuminate the study of curriculum and guide the design of curricula. (Author/RK)

  20. Intelligent tutoring systems for systems engineering methodologies

    NASA Technical Reports Server (NTRS)

    Meyer, Richard J.; Toland, Joel; Decker, Louis

    1991-01-01

    The general goal is to provide the technology required to build systems that can provide intelligent tutoring in IDEF (Integrated Computer Aided Manufacturing Definition Method) modeling. The following subject areas are covered: intelligent tutoring systems for systems analysis methodologies; IDEF tutor architecture and components; developing cognitive skills for IDEF modeling; experimental software; and PC based prototype.

  1. Systems Measures of Water Distribution System Resilience

    SciTech Connect

    Klise, Katherine A.; Murray, Regan; Walker, La Tonya Nicole

    2015-01-01

    Resilience is a concept that is being used increasingly to refer to the capacity of infrastructure systems to be prepared for and able to respond effectively and rapidly to hazardous events. In Section 2 of this report, drinking water hazards, resilience literature, and available resilience tools are presented. Broader definitions, attributes and methods for measuring resilience are presented in Section 3. In Section 4, quantitative systems performance measures for water distribution systems are presented. Finally, in Section 5, the performance measures and their relevance to measuring the resilience of water systems to hazards is discussed along with needed improvements to water distribution system modeling tools.

  2. Lighting system with thermal management system

    DOEpatents

    Arik, Mehmet; Weaver, Stanton; Stecher, Thomas; Seeley, Charles; Kuenzler, Glenn; Wolfe, Jr., Charles; Utturkar, Yogen; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2013-05-07

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  3. Lighting system with thermal management system

    DOEpatents

    Arik, Mehmet; Weaver, Stanton Earl; Stecher, Thomas Elliot; Seeley, Charles Erklin; Kuenzler, Glenn Howard; Wolfe, Jr., Charles Franklin; Utturkar, Yogen Vishwas; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2015-08-25

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  4. Lighting system with thermal management system

    DOEpatents

    Arik, Mehmet; Weaver, Stanton Earl; Stecher, Thomas Elliot; Seeley, Charles Erklin; Kuenzler, Glenn Howard; Wolfe, Jr, Charles Franklin; Utturkar, Yogen Vishwas; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2016-10-11

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  5. Lighting system with thermal management system

    DOEpatents

    Arik, Mehmet; Weaver, Stanton Earl; Stecher, Thomas Elliot; Seeley, Charles Erklin; Kuenzler, Glenn Howard; Wolfe, Jr., Charles Franklin; Utturkar, Yogen Vishwas; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2015-02-24

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  6. Microwave landing system autoland system analysis

    NASA Technical Reports Server (NTRS)

    Feather, J. B.; Craven, B. K.

    1991-01-01

    The objective was to investigate the ability of present day aircraft equipped with automatic flight control systems to fly advanced Microwave Landing Systems (MLS) approaches. The tactical approach used to achieve this objective included reviewing the design and autoland operation of the MD-80 aircraft, simulating the MLS approaches using a batch computer program, and assessing the performance of the autoland system from computer generated data. The results showed changes were required to present Instrument Landing System (ILS) procedures to accommodate the new MLS curved paths. It was also shown that in some cases, changes to the digital flight guidance systems would be required so that an autoland could be performed.

  7. DDL system: Design systhesis of digital systems

    NASA Technical Reports Server (NTRS)

    Shiva, S. G.

    1983-01-01

    Digital Systems Design Language was integrated into the CADAT system environment of NASA-MSFC. The major technical aspects of this integration are summarized. Automatic hardware synthesis is now possible starting with a high level description of the system to be synthesized. The DDL system provides a high level design verification capability, thereby minimizing design changes in the later stages of the design cycle. An overview of the DDL system covering the translation, simulation and synthesis capabilities is provided. Two companion documents (the user's and programmer's manuals) are to be consulted for detailed discussions.

  8. Root production method system

    Treesearch

    Wayne Lovelace

    2002-01-01

    The RPM system (Root Production Method) is a multistep production system of container tree production that places primary emphasis on the root system because the root system ultimately determines the tree's survival and performance in its outplanted environment. This particular container production system has been developed to facilitate volume production, in a...

  9. Systems Engineering Measurement Primer

    DTIC Science & Technology

    1998-03-01

    Systems Engineering Measurement Primer A Basic Introduction to Systems Engineering Measurement Concepts and Use Version 1.0 March 1998 This document...Federal Systems Garry Roedler Lockheed Martin Management & Data Systems Cathy Tilton The National Registry, Inc. E. Richard Widmann Raytheon Systems...IV 1. INTRODUCTION

  10. Intelligent test integration system

    NASA Technical Reports Server (NTRS)

    Sztipanovits, J.; Padalkar, S.; Rodriguez-Moscoso, J.; Kawamura, K.; Purves, B.; Williams, R.; Biglari, H.

    1988-01-01

    A new test technology is described which was developed for space system integration. The ultimate purpose of the system is to support the automatic generation of test systems in real time, distributed computing environments. The Intelligent Test Integration System (ITIS) is a knowledge based layer above the traditional test system components which can generate complex test configurations from the specification of test scenarios.

  11. Immune System 101

    MedlinePlus

    ... Immune System 101 Subscribe Translate Text Size Print Immune System 101 How Does Your Immune System Work? Your immune system works because your body ... tactics to destroy it. Major Players of the Immune System Lymph nodes (also called "lymph glands"): These small, ...

  12. Selecting Authoring Systems.

    ERIC Educational Resources Information Center

    Locatis, Craig; Carr, Victor

    1985-01-01

    Presents suggestions for selecting authoring systems based on reviews of over one dozen systems; defines authoring systems; discusses their potential benefits; introduces background evaluation concepts; describes procedures for collecting information about system attributes; and presents a system selection checklist and an authoring system…

  13. Systems Intelligence Inventory

    ERIC Educational Resources Information Center

    Törmänen, Juha; Hämäläinen, Raimo P.; Saarinen, Esa

    2016-01-01

    Purpose: Systems intelligence (SI) (Saarinen and Hämäläinen, 2004) is a construct defined as a person's ability to act intelligently within complex systems involving interaction and feedback. SI relates to our ability to act in systems and reason about systems to adaptively carry out productive actions within and with respect to systems such as…

  14. Control and dynamic systems

    SciTech Connect

    Leondes, C.T. . Dept. of Electrical Engineering)

    1991-01-01

    This volume covers topics related to analysis and control system techniques for electric power systems. Topics include: simulation of multimachine power system dynamics, computer simulation in electric distribution systems, transient stability assessment, dynamic stability analysis, and improved power system control techniques.

  15. Systems Intelligence Inventory

    ERIC Educational Resources Information Center

    Törmänen, Juha; Hämäläinen, Raimo P.; Saarinen, Esa

    2016-01-01

    Purpose: Systems intelligence (SI) (Saarinen and Hämäläinen, 2004) is a construct defined as a person's ability to act intelligently within complex systems involving interaction and feedback. SI relates to our ability to act in systems and reason about systems to adaptively carry out productive actions within and with respect to systems such as…

  16. Collaborative Systems Testing

    ERIC Educational Resources Information Center

    Pocatilu, Paul; Ciurea, Cristian

    2009-01-01

    Collaborative systems are widely used today in various activity fields. Their complexity is high and the development involves numerous resources and costs. Testing collaborative systems has a very important role for the systems' success. In this paper we present taxonomy of collaborative systems. The collaborative systems are classified in many…

  17. The LSST: A System of Systems

    NASA Astrophysics Data System (ADS)

    Claver, Chuck F.; Debois-Felsmann, G. P.; Delgado, F.; Hascall, P.; Marshall, S.; Nordby, M.; Schumacher, G.; Sebag, J.; LSST Collaboration

    2011-01-01

    The Large Synoptic Survey Telescope (LSST) is a complete observing system that acquires and archives images, processes and analyzes them, and publishes reduced images and catalogs of sources and objects. The LSST will operate over a ten year period producing a survey of 20,000 square degrees over the entire [Southern] sky in 6 filters (ugrizy) with each field having been visited several hundred times enabling a wide spectrum of science from fast transients to exploration of dark matter and dark energy. The LSST itself is a complex system of systems consisting of the 8.4m 3-mirror telescope, a 3.2 billion pixel camera, and a peta-scale data management system. The LSST project uses a Model Based Systems Engineering (MBSE) methodology to ensure an integrated approach to system design and rigorous definition of system interfaces and specifications. The MBSE methodology is applied through modeling of the LSST's systems with the System Modeling Language (SysML). The SysML modeling recursively establishes the threefold relationship between requirements, logical & physical functional decomposition and definition, and system and component behavior at successively deeper level of abstraction and detail. The LSST modeling includes the analysis and documenting the flow of command and control information and data between the suite of systems in the LSST observatory that are needed to carry out the activities of the survey. The MBSE approach is applied throughout all stages of the project from design, to validation and verification, though to commissioning.

  18. Systems Architecture for a Nationwide Healthcare System.

    PubMed

    Abin, Jorge; Nemeth, Horacio; Friedmann, Ignacio

    2015-01-01

    From a national level to give Internet technology support, the Nationwide Integrated Healthcare System in Uruguay requires a model of Information Systems Architecture. This system has multiple healthcare providers (public and private), and a strong component of supplementary services. Thus, the data processing system should have an architecture that considers this fact, while integrating the central services provided by the Ministry of Public Health. The national electronic health record, as well as other related data processing systems, should be based on this architecture. The architecture model described here conceptualizes a federated framework of electronic health record systems, according to the IHE affinity model, HL7 standards, local standards on interoperability and security, as well as technical advice provided by AGESIC. It is the outcome of the research done by AGESIC and Systems Integration Laboratory (LINS) on the development and use of the e-Government Platform since 2008, as well as the research done by the team Salud.uy since 2013.

  19. Efficacy of focal mechanic vibration treatment on balance in Charcot-Marie-Tooth 1A disease: a pilot study.

    PubMed

    Pazzaglia, Costanza; Camerota, F; Germanotta, M; Di Sipio, E; Celletti, C; Padua, L

    2016-07-01

    Patients affected by Charcot-Marie-Tooth (CMT) disease experience an impaired balance. Although the causes of the postural instability are not fully understood, somatosensory system seems to play a key role. Mechanical vibration seems to act on the somatosensory system and to improve its function. The aim of our study was to evaluate the effects of focal mechanical vibration (fMV) on the balance of CMT 1A patients. We enrolled 14 genetically confirmed CMT 1A patients (8 female and 6 male, mean age 492 years, range 32-74, mean duration of disease: 13 years, range 1-30). Patients underwent a 3-day fMV treatment on quadriceps and triceps surae and were evaluated before the treatment as well as 1 week and 1 month after the end of the treatment. The primary outcome measure was the Berg Balance Scale (BBS) and the secondary were the Dynamic Gait Index (DGI), the 6 Min Walking Test (6MWT), the muscular strength of lower limbs, the Quality of Life (QoL) questionnaire and the stabilometric variables. The statistical analysis showed a significant modification of the BBS due to the effect of treatment (p < 0.05). A significant modification was also found in the DGI (p < 0.05). Concerning the stabilometric variables we found significant changes only for the eyes closed condition; in particular, a significant decrease was found in VelocityML (p < 0.05) and Sway path length (p < 0.05). The fMV treatment applied on lower limbs of CMT 1A patients determined an improvement of balance as detected by the BBS. The concurrent improvement of stabilometric variables in the eyes closed condition only suggests that fMV acts mostly on somatosensory afferences. Further studies are needed to confirm these data on a larger sample of CMT patients.

  20. Evaluating a Portfolio System.

    ERIC Educational Resources Information Center

    Smit, David W.

    1990-01-01

    Contributes to the knowledge of portfolio systems for writing evaluation by sharing evaluative procedures and their results. Reports on the results of a survey of students evaluated using a portfolio system. Finds that students preferred the portfolio system. (RS)

  1. Autonomic Nervous System Disorders

    MedlinePlus

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart and ... blood vessels. When something goes wrong in this system, it can cause serious problems, including Blood pressure ...

  2. Alternative Videodisc Systems.

    ERIC Educational Resources Information Center

    Heath, Ted

    1981-01-01

    Discusses consumer and industrial videodisc systems for information storage including cost, technology utilized, formats, and features. Reflective and transmissive laser optical systems are described, as well as the grooved and grooveless mechanical systems. Tables containing product data are included. (JJD)

  3. Male Reproductive System

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Male Reproductive System KidsHealth > For Parents > Male Reproductive System A A ... your son's reproductive health. continue About the Male Reproductive System Most species have two sexes: male and female. ...

  4. Air cushion landing system

    NASA Technical Reports Server (NTRS)

    Boghami, K. M.; Captain, K. M.; Fish, R. B.

    1978-01-01

    Static and dynamic performance of air cushion landing system is simulated in computer program that treats four primary ACLS subsystems: fan, feeding system, trunk, and cushion. Configuration of systems is sufficiently general to represent variety of practical designs.

  5. Wind energy systems

    NASA Technical Reports Server (NTRS)

    Stewart, H. J.

    1978-01-01

    A discussion on wind energy systems involved with the DOE wind energy program is presented. Some of the problems associated with wind energy systems are discussed. The cost, efficiency, and structural design of wind energy systems are analyzed.

  6. Multiple System Atrophy (MSA)

    MedlinePlus

    Multiple system atrophy (MSA) Overview By Mayo Clinic Staff Multiple system atrophy (MSA) is a rare, degenerative neurological disorder ... progresses gradually and eventually leads to death. Multiple system atrophy care at Mayo Clinic . Mayo Clinic Footer ...

  7. The Trinity System

    SciTech Connect

    Archer, Billy Joe; Vigil, Benny Manuel

    2015-01-13

    This paper describes the Trinity system, the first ASC Advanced Technology System (ATS-1). We describe the Trinity procurement timeline, the ASC computing strategy, the Trinity specific mission needs, and the Trinity system specifications.

  8. Lungs and Respiratory System

    MedlinePlus

    ... Your 1- to 2-Year-Old Lungs and Respiratory System KidsHealth > For Parents > Lungs and Respiratory System A ... ll have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't happen ...

  9. Manned systems technology discipline

    NASA Technical Reports Server (NTRS)

    Bretoi, Remus

    1990-01-01

    Viewgraphs on manned systems technology discipline for Space Station Freedom are presented. Topics covered include: crew-systems interfaces and interactions; crew training; on-board systems maintenance and support; habitability and environment; and computational human factors.

  10. TWRSview system requirements specification

    SciTech Connect

    Caldwell, J.A.; Lee, A.K.

    1995-12-01

    This document provides the system requirements specification for the TWRSview software system. The TWRSview software system is being developed to integrate electronic data supporting the development of the TWRS technical baseline

  11. Air cushion landing system

    NASA Technical Reports Server (NTRS)

    Boghami, K. M.; Captain, K. M.; Fish, R. B.

    1978-01-01

    Static and dynamic performance of air cushion landing system is simulated in computer program that treats four primary ACLS subsystems: fan, feeding system, trunk, and cushion. Configuration of systems is sufficiently general to represent variety of practical designs.

  12. What Are Expert Systems?

    ERIC Educational Resources Information Center

    d'Agapeyeff, A.

    1986-01-01

    Intended for potential business users, this paper describes the main characteristics of expert systems; discusses practical use considerations; presents a taxonomy of the systems; and reviews several expert system development projects in business and industry. (MBR)

  13. Multivariable Control Systems

    DTIC Science & Technology

    1968-01-01

    one). Examples abound of systems with numerous controlled variables, and the modern tendency is toward ever greater utilization of systems and plants of this kind. We call them multivariable control systems (MCS).

  14. Antiskid braking system

    NASA Technical Reports Server (NTRS)

    Pazdera, J. S.

    1974-01-01

    Published report describes analytical development and simulation of braking system. System prevents wheels from skidding when brakes are applied, significantly reducing stopping distance. Report also presents computer simulation study on system as applied to aircraft.

  15. Immune System Quiz

    MedlinePlus

    ... Room? What Happens in the Operating Room? Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  16. Digestive System (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Digestive System KidsHealth > For Teens > Digestive System A A A ... out of the body as feces. About the Digestive System Every morsel of food we eat has to ...

  17. The LSST: A System of Systems

    NASA Astrophysics Data System (ADS)

    Claver, Chuck F.; Dubois-Felsmann, G. P.; Delgado, F.; Hascall, P.; Horn, D.; Marshall, S.; Nordby, M.; Schalk, T. L.; Schumacher, G.; Sebag, J.; LSST Project Team

    2010-01-01

    The LSST is a complete observing system that acquires and archives images, processes and analyzes them, and publishes reduced images and catalogs of sources and objects. The LSST will operate over a ten year period producing a survey of 20,000 square degrees over the entire southern sky in 6 filters (ugrizy) with each field having been visited several hundred times enabling a wide spectrum of science from fast transients to exploration of dark matter and dark energy. The LSST itself is a complex system of systems consisting of the 8.4m three mirror telescope, a 3.2 billion pixel camera, and a peta-scale data management system. The LSST project uses a Model Based Systems Engineering (MBSE) methodology to ensure an integrated approach to system design and rigorous definition of system interfaces and specifications. The MBSE methodology is applied through modeling of the LSST's systems with the System Modeling Language (SysML). The SysML modeling recursively establishes the threefold relationship between requirements, logical & physical functional decomposition and definition, and system and component behavior at successively deeper levels of abstraction and detail. The MBSE approach is applied throughout all stages of the project from design, to validation and verification, though to commissioning.

  18. Propulsion Systems Panel deliberations

    NASA Technical Reports Server (NTRS)

    Bianca, Carmelo J.; Miner, Robert; Johnston, Lawrence M.; Bruce, R.; Dennies, Daniel P.; Dickenson, W.; Dreshfield, Robert; Karakulko, Walt; Mcgaw, Mike; Munafo, Paul M.

    1993-01-01

    The Propulsion Systems Panel was established because of the specialized nature of many of the materials and structures technology issues related to propulsion systems. This panel was co-chaired by Carmelo Bianca, MSFC, and Bob Miner, LeRC. Because of the diverse range of missions anticipated for the Space Transportation program, three distinct propulsion system types were identified in the workshop planning process: liquid propulsion systems, solid propulsion systems and nuclear electric/nuclear thermal propulsion systems.

  19. Systems interface biology

    PubMed Central

    Doyle, Francis J; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines. PMID:16971329

  20. System status display information

    NASA Technical Reports Server (NTRS)

    Summers, L. G.; Erickson, J. B.

    1984-01-01

    The system Status Display is an electronic display system which provides the flight crew with enhanced capabilities for monitoring and managing aircraft systems. Guidelines for the design of the electronic system displays were established. The technical approach involved the application of a system engineering approach to the design of candidate displays and the evaluation of a Hernative concepts by part-task simulation. The system engineering and selection of candidate displays are covered.

  1. Systems interface biology.

    PubMed

    Doyle, Francis J; Stelling, Jörg

    2006-10-22

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines.

  2. Endocrine System (For Parents)

    MedlinePlus

    ... System The major glands that make up the human endocrine system are the hypothalamus, pituitary, thyroid, parathyroids, adrenals, pineal body, and the reproductive glands, which include the ovaries ...

  3. Control system design method

    DOEpatents

    Wilson, David G [Tijeras, NM; Robinett, III, Rush D.

    2012-02-21

    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  4. Lightside Atmospheric Revitalization System

    NASA Technical Reports Server (NTRS)

    Colling, A. K.; Cushman, R. J.; Hultman, M. M.; Nason, J. R.

    1980-01-01

    The system was studied as a replacement to the present baseline LiOH system for extended duration shuttle missions. The system consists of three subsystems: a solid amine water desorbed regenerable carbon dioxide removal system, a water vapor electrolysis oxygen generating system, and a Sabatier reactor carbon dioxide reduction system. The system is designed for use on a solar powered shuttle vehicle. The majority of the system's power requirements are utilized on the Sun side of each orbit, when solar power is available.

  5. Umbra's system representation.

    SciTech Connect

    McDonald, Michael James

    2005-07-01

    This document describes the Umbra System representation. Umbra System representation, initially developed in the spring of 2003, is implemented in Incr/Tcl using concepts borrowed from Carnegie Mellon University's Architecture Description Language (ADL) called Acme. In the spring of 2004 through January 2005, System was converted to Umbra 4, extended slightly, and adopted as the underlying software system for a variety of Umbra applications that support Complex Systems Engineering (CSE) and Complex Adaptive Systems Engineering (CASE). System is now a standard part Of Umbra 4. While Umbra 4 also includes an XML parser for System, the XML parser and Schema are not described in this document.

  6. Systems engineering for very large systems

    NASA Technical Reports Server (NTRS)

    Lewkowicz, Paul E.

    1993-01-01

    Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

  7. Systems engineering for very large systems

    NASA Astrophysics Data System (ADS)

    Lewkowicz, Paul E.

    Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

  8. Expert system requirements for power system restoration

    SciTech Connect

    Adibi, M.M. ); Kafka, R.J. ); Milanicz, D.P. )

    1994-08-01

    This paper is one of series presented on behalf of the System Operation Subcommittee with the intent of focusing industry attention on power system restoration. Expert systems are being considered for restoring bulk power supplies. In general, there are three restoration periods following a major power disturbance: establishment of initial sources of power, re-integration of a skeleton of the bulk power supply, and minimization of the unserved loads. Expert systems together with analytical tools have the potential of addressing the restoration procedures over these three periods. This paper describes the expert system requirements from the point of view of the practicing power engineers with emphasis placed on the initial power sources and requirements. The paper draws on the previous reports by the Power System Restoration Working Group.

  9. Epilogue: Systems Approaches and Systems Practice

    NASA Astrophysics Data System (ADS)

    Reynolds, Martin; Holwell, Sue

    Each of the five systems approaches discussed in this volume: system dynamics (SD), the viable systems model (VSM), strategic options development and analysis (SODA), soft systems methodology (SSM) and critical systems heuristics (CSH) has a pedigree. Not in the sense of the sometimes absurd spectacle of animals paraded at dog shows. Rather, their pedigree derives from their systems foundations, their capacity to evolve and their flexibility in use. None of the five approaches has developed out of use in restricted and controlled contexts of either low or high levels of complicatedness. Neither has any one of them evolved as a consequence of being applied only to situations with either presumed stakeholder agreement on purpose, or courteous disagreement amongst stakeholders, or stakeholder coercion. The compilation is not a celebration of abstract ‘methodologies', but of theoretically robust approaches that have a genuine pedigree in practice.

  10. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  11. Development of Cd1-xMgxTe thin films for application as an electron reflector in CdS/CdTe solar cells

    NASA Astrophysics Data System (ADS)

    Kobyakov, Pavel S.

    Efficiencies of CdS/CdTe photovoltaic cells significantly lag behind their theoretical limit, primarily because open-circuit voltage ( VOC) of record efficiency cells (872 mV) is well below what is expected for the CdTe band gap (1.5 eV). A substantial V OC improvement can be achieved through addition of an electron reflector (ER) layer to CdTe devices. The ER layer forms a conduction-band barrier that reflects minority-charge carriers (i.e. electrons in p-type CdTe) away from the back surface. Similar to back-surface fields in c-Si, III-V, and CIGS solar cells, the ER strategy is expected to reduce back-surface recombination and is estimated to increase CdTe VOC by about 200 mV based on numerical simulation. The presented research investigates the addition of a thin layer of wider band gap Cd1-xMgxTe (CMT) to achieve a CdTe ER structure. First, a novel co-sublimation process was developed for deposition of Cd 1-xMgxTe thin films that demonstrates excellent experimental capabilities, commercial viability, and improved alloy control over other techniques. Next, the effects of processing on material properties of CMT deposition onto CdS/CdTe structures were investigated. It was discovered that substrate temperature during CMT deposition is a critical parameter for achieving uniform CMT film coverage on polycrystalline CdTe. Furthermore, CMT film growth was found to be epitaxial on CdTe where the CMT films retain the same microstructural features as the underlying CdTe grains. Despite film uniformity, significant Mg loss from the CMT film, oxide formation, and a reduction of the optical band gap was found after CdCl2-based passivation treatments. Preliminary process optimization found that band gap degradation can be minimized by utilizing MgCl2 in addition to CdCl2 as a treatment source material. Finally, development of CdS/CdTe/Cd1-xMgxTe electron reflector devices demonstrated a barrier behavior at high voltage bias and improved voltage when CdTe thickness is held

  12. Embedding Cognitive Systems into Systems Engineering Practice

    DTIC Science & Technology

    2008-12-01

    performing knowledge elicitation, task analyses, or workload and manpower assessments , as examples. Contrast a systems engineering simulation, a computer...aid. The product can be used to depict scripted human interactions with products. Its engine underpins the Imprint human systems integration tool...like CIOs decide what users need and their opinions, not user demand, dictate system characteristics. What should be an assessment of functional

  13. Survivability Assurance for System of Systems

    DTIC Science & Technology

    2008-05-01

    power grid failure in the northeastern United States and Canada in the summer of 2003 is another recent example of the effects of a system failure... effect of failures on the customs network. The power grid failure was not caused by a single event but by a cascading set of failures, including a...respond to change may result in un- intended side effects , not only to the constituent system but to other systems as well. For example, the addition of

  14. INSENS sensor system

    SciTech Connect

    Myers, D.W.; Baker, J.; Benzel, D.M.; Fuess, D.A.

    1993-09-29

    This paper describes an unattended ground sensor system that has been developed for the immigration and Naturalization Service (INS). The system, known as INSENS, was developed at the Lawrence Livermore National Laboratory for use by the United States Border Patrol. This system assists in the detection of illegal entry of aliens and contraband (illegal drugs, etc.) into the United States along its land borders. Key to the system is its flexible modular design which allows future software and hardware enhancements to the system without altering the fundamental architecture of the system. Elements of the system include a sensor system capable of processing signals from multiple directional probes, a repeater system, and a handheld monitor system. Seismic, passive infrared (PIR), and magnetic probes are currently supported. The design of the INSENS system elements and their performance are described.

  15. Precision digital control systems

    NASA Astrophysics Data System (ADS)

    Vyskub, V. G.; Rozov, B. S.; Savelev, V. I.

    This book is concerned with the characteristics of digital control systems of great accuracy. A classification of such systems is considered along with aspects of stabilization, programmable control applications, digital tracking systems and servomechanisms, and precision systems for the control of a scanning laser beam. Other topics explored are related to systems of proportional control, linear devices and methods for increasing precision, approaches for further decreasing the response time in the case of high-speed operation, possibilities for the implementation of a logical control law, and methods for the study of precision digital control systems. A description is presented of precision automatic control systems which make use of electronic computers, taking into account the existing possibilities for an employment of computers in automatic control systems, approaches and studies required for including a computer in such control systems, and an analysis of the structure of automatic control systems with computers. Attention is also given to functional blocks in the considered systems.

  16. System of systems modeling and simulation.

    SciTech Connect

    Lawton, Craig R.; Campbell, James E.; Anderson, Dennis James; Thompson, Bruce Miles; Longsine, Dennis E.; Shirah, Donald N.; Cranwell, Robert M.

    2005-02-01

    Analyzing the performance of a complex System of Systems (SoS) requires a systems engineering approach. Many such SoS exist in the Military domain. Examples include the Army's next generation Future Combat Systems 'Unit of Action' or the Navy's Aircraft Carrier Battle Group. In the case of a Unit of Action, a system of combat vehicles, support vehicles and equipment are organized in an efficient configuration that minimizes logistics footprint while still maintaining the required performance characteristics (e.g., operational availability). In this context, systems engineering means developing a global model of the entire SoS and all component systems and interrelationships. This global model supports analyses that result in an understanding of the interdependencies and emergent behaviors of the SoS. Sandia National Laboratories will present a robust toolset that includes methodologies for developing a SoS model, defining state models and simulating a system of state models over time. This toolset is currently used to perform logistics supportability and performance assessments of the set of Future Combat Systems (FCS) for the U.S. Army's Program Manager Unit of Action.

  17. Hot Spot Removal System: System description

    SciTech Connect

    1997-09-01

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

  18. Immune System as a Sensory System

    PubMed Central

    Dozmorov, Igor M.; Dresser, D.

    2010-01-01

    As suggested by the well-known gestalt concept the immune system can be regarded as an integrated complex system, the functioning of which cannot be fully characterized by the behavior of its constituent elements. Similar approaches to the immune system in particular and sensory systems in general allows one to discern similarities and differences in the process of distinguishing informative patterns in an otherwise random background, thus initiating an appropriate and adequate response. This may lead to a new interpretation of difficulties in the comprehension of some immunological phenomena. PMID:21686066

  19. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  20. Broad Bandwidth Telecommunications Systems.

    ERIC Educational Resources Information Center

    Sodolski, John

    Broad bandwidth transmission systems have been around for years. They include microwave, assorted cable systems, and recently, satellites. With the exception of some privately owned systems, broadband services have been furnished by the common carriers. Recently, a new element has been added--Cable Antenna Television (CATV) distribution systems.…