WorldWideScience

Sample records for volume 2-b shelby

  1. Bathymetric Contours for Prairie Rose Lake, Shelby County, Iowa

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digital bathymetry contours for Prairie Rose Lake in Shelby Co., Iowa. The U.S. Geological Survey conducted a bathymetric survey of...

  2. Parcels and Land Ownership, Published in 2011, Shelby County Government.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Parcels and Land Ownership dataset as of 2011. The extent of these data is generally Shelby County, IA. This metadata was auto-generated through the Ramona GIS...

  3. Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers

    DEFF Research Database (Denmark)

    Eskildsen, Simon F; Østergaard, Lasse R; Rodell, Anders B;

    2008-01-01

    Frontotemporal dementia constitutes the third most prevalent neurodegenerative disease with dementia. We compared cortical structural changes in nine presymptomatic CHMP2B frontotemporal dementia mutation positive individuals with seven mutation negative family members. Using serial MRI scans...... with a mean interval of 16 months and surface based cortical segmentation we measured cortical thickness and volume, and quantified atrophy rates. Cortical thickness and atrophy rates were averaged within major lobes and focal effects were determined by parametric statistical maps. The volumetric atrophy...... rates in the presymptomatic CHMP2B mutation carriers were statistically significant, though of a lower magnitude than those previously reported in patients of other types of frontotemporal dementia. Cortical thickness measurements revealed cortical thinning in mutation carriers bilaterally...

  4. Thrilling but Pointless: General JO Shelby’s 1863 Cavalry Raid

    Science.gov (United States)

    2013-12-13

    Carolina.5 Here Shelby used slave labor to raise hemp for rope manufacturing, a vital asset to the South who needed the rope to bind their cotton bales...of his book. Edwards used his occupation as a newspaper editor in Kansas City, Missouri, as a further platform to drive his opinions of the...cousin, Isaac Shelby. Shelby’s father, Orville Shelby, was a wealthy plantation owner and prospered in the hemp business.2 Shelby’s father died when

  5. Hydrologic and hydraulic analyses for the Black Fork Mohican River Basin in and near Shelby, Ohio

    Science.gov (United States)

    Huitger, Carrie A.; Ostheimer, Chad J.; Koltun, G.F.

    2016-05-06

    Hydrologic and hydraulic analyses were done for selected reaches of five streams in and near Shelby, Richland County, Ohio. The U.S. Geological Survey (USGS), in cooperation with the Muskingum Watershed Conservancy District, conducted these analyses on the Black Fork Mohican River and four tributaries: Seltzer Park Creek, Seltzer Park Tributary, Tuby Run, and West Branch. Drainage areas of the four stream reaches studied range from 0.51 to 60.3 square miles. The analyses included estimation of the 10-, 2-, 1-, and 0.2-percent annual-exceedance probability (AEP) flood-peak discharges using the USGS Ohio StreamStats application. Peak discharge estimates, along with cross-sectional and hydraulic structure geometries, and estimates of channel roughness coefficients were used as input to step-backwater models. The step-backwater water models were used to determine water-surface elevation profiles of four flood-peak discharges and a regulatory floodway. This study involved the installation of, and data collection at, a streamflow-gaging station (Black Fork Mohican River at Shelby, Ohio, 03129197), precipitation gage (Rain gage at Reservoir Number Two at Shelby, Ohio, 405209082393200), and seven submersible pressure transducers on six selected river reaches. Two precipitation-runoff models, one for the winter events and one for nonwinter events for the headwaters of the Black Fork Mohican River, were developed and calibrated using the data collected. With the exception of the runoff curve numbers, all other parameters used in the two precipitation-runoff models were identical. The Nash-Sutcliffe model efficiency coefficients were 0.737, 0.899, and 0.544 for the nonwinter events and 0.850 and 0.671 for the winter events. Both of the precipitation-runoff models underestimated the total volume of water, with residual runoff ranging from -0.27 inches to -1.53 inches. The results of this study can be used to assess possible mitigation options and define flood hazard areas that

  6. Data-Collection Points Along Transects and Around Perimeter at Prairie Rose Lake, Shelby County, Iowa

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Point coverage of bathymetry data for Prairie Rose Lake in Shelby Co., Iowa. The U.S. Geological Survey conducted a bathymetric survey of Prairie Rose Lake in 2004.

  7. GRIN2B encephalopathy

    DEFF Research Database (Denmark)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah

    2017-01-01

    presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense...... treatment response in the respective patients still remains to be demonstrated. CONCLUSIONS: In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment...

  8. Proceedings of the Annual Conference on Magnetism and Magnetic Materials (37th) Held in Houston, Texas on 1-4 December 1993. Pages 5309-6146. Journal of Applied Physics. Volume 73. Number 10, Part 2 B,

    Science.gov (United States)

    Reprint: Proceedings of the Annual Conference on Magnetism and Magnetic Materials (37th) Held in Houston, Texas on 1-4 December 1993. Pages 5309-6146. Journal of Applied Physics . Volume 73. Number 10, Part 2 B,

  9. 77 FR 24200 - American Drum & Pallet, Memphis, Shelby County, TN; Notice of Settlement

    Science.gov (United States)

    2012-04-23

    ... AGENCY American Drum & Pallet, Memphis, Shelby County, TN; Notice of Settlement AGENCY: Environmental... settlement for reimbursement of past response costs concerning the American Drum and Pallet Superfund Site...-04- 2012-3770 or Site name American Drum & Pallet Superfund Site by one of the following methods: www...

  10. 77 FR 47840 - American Drum and Pallet Company Site; Memphis, Shelby County, Tennessee; Notice of settlement

    Science.gov (United States)

    2012-08-10

    ... AGENCY American Drum and Pallet Company Site; Memphis, Shelby County, Tennessee; Notice of settlement... Agency has entered into a settlement for past response costs concerning the American Drum and Pallet... Drum and Pallet Company Site by one of the following methods: www.epa.gov/region4/superfund/programs...

  11. 76 FR 13667 - Commercial Furniture Group, Inc., Formerly Known as Falcon Products, Inc., Shelby Williams, Howe...

    Science.gov (United States)

    2011-03-14

    ..., Inc., Shelby Williams, Howe and Thonet, Including On-Site Leased Workers From Staffing Solutions... Williams, Howe and Thonet, Chicago, IL; Amended Certification Regarding Eligibility To Apply for Worker... Williams, Howe and Thonet. New information shows that some workers separated from employment at...

  12. "Shelby County v. Holder": What It Means for the Voting Rights Act

    Science.gov (United States)

    Schwinn, Steven D.

    2013-01-01

    This summer, the U.S. Supreme Court ruled in "Shelby County v. Holder" that Congress had exceeded its Fifteenth Amendment enforcement authority when it reauthorized a part of the Voting Rights Act (a coverage formula) that forced places with a history of discrimination to get federal approval before making changes to their election laws.…

  13. Individual Target Data-Collection Points Upstream of the Siltation Dam at Prairie Rose Lake, Shelby County, Iowa

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Point coverage of bathymetry target points upstream of the siltation dam at Prairie Rose Lake in Shelby Co., Iowa. The U.S. Geological Survey conducted a...

  14. Individual Target Data-Collection Points for the Main Portion of Prairie Rose Lake, Shelby County, Iowa

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Point coverage of bathymetry target points for the main portion of Prairie Rose Lake in Shelby Co., Iowa. The U.S. Geological Survey conducted a bathymetric survey...

  15. Notes from the Field: Measles Outbreak of Unknown Source - Shelby County, Tennessee, April-May 2016.

    Science.gov (United States)

    Fill, Mary-Margaret A; Sweat, David; Morrow, Helen; Haushalter, Alisa; Martin, Judy C; Zerwekh, Tyler; Chakraverty, Tamal; Kmet, Jennifer; Morris, Kevin; Moore, Kelly; Kainer, Marion; Murphree, Rendi; Dunn, John R; Schaffner, William; Jones, Timothy F

    2016-09-30

    On April 15, 2016, local public health officials in Shelby County, Tennessee, were notified of a positive measles immunoglobulin M (IgM) test for a male aged 18 months (patient A). On April 18, 2016, a second positive measles IgM test was reported for a man aged 50 years (patient B). Both patients had rash onset on April 9, 2016. The Shelby County Health Department initiated an investigation, and confirmatory testing for measles virus on oropharyngeal swabs by polymerase chain reaction (PCR) at CDC was positive for both patients. On April 21, 2016, public health officials were notified of a third suspected measles case in a female aged 7 months (patient C) who had developed a rash on April 14; PCR testing was positive. Genotyping conducted at CDC identified genotype B3 measles virus in all three cases. Genotype B3 is known to be circulating globally and has previously been associated with imported cases in the United States (1).

  16. Geotechnical Analysis of Five Shelby Tube Samples from H-Area Retention Basin

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.A.

    1999-06-02

    Geotechnical and geochemical analyses were performed on five Shelby tube samples collected in the H-Area Retention Basin (HRB) during July and August of 1998. The samples were collected as part of the HRB characterization study. The test results, which are documented in this report, will be used to support the HRB contaminant fate and transport modeling/analysis and to evaluate remedial options. The results will also be used as a base line for future treatability studies.

  17. B2B marketing

    OpenAIRE

    Pospíšilová, Lucie

    2010-01-01

    The main goal of this bachelor thesis is to apply theoretical knowledge in B2B marketing to the example of marketing processes in a particular company, to evaluate the current situation of its activities with regard to B2B principles and to suggest relevant recommendations. The theoretical part focuses on specific characteristics of B2B marketing, describes its differences from marketing on consumer markets, deals with buying behaviour of organizations and specifies particular features of mar...

  18. Data Catalog Series for Space Science and Applications Flight Missions. Volume 2B; Descriptions of Data Sets from Geostationary and High-Altitude Scientific Spacecraft and Investigations

    Science.gov (United States)

    Schofield, Norman J. (Editor); Parthasarathy, R. (Editor); Hills, H. Kent (Editor)

    1988-01-01

    The main purpose of the data catalog series is to provide descriptive references to data generated by space science flight missions. The data sets described include all of the actual holdings of the Space Science Data Center (NSSDC), all data sets for which direct contact information is available, and some data collections held and serviced by foreign investigators, NASA and other U.S. government agencies. This volume contains narrative descriptions of data sets from geostationary and high altitude scientific spacecraft and investigations. The following spacecraft series are included: Mariner, Pioneer, Pioneer Venus, Venera, Viking, Voyager, and Helios. Separate indexes to the planetary and interplanetary missions are also provided.

  19. Gulf Coast geopressured-geothermal program summary report compilation. Volume 2-B: Resource description, program history, wells tested, university and company based research, site restoration

    Energy Technology Data Exchange (ETDEWEB)

    John, C.J.; Maciasz, G.; Harder, B.J.

    1998-06-01

    The US Department of Energy established a geopressured-geothermal energy program in the mid 1970`s as one response to America`s need to develop alternate energy resources in view of the increasing dependence on imported fossil fuel energy. This program continued for 17 years and approximately two hundred million dollars were expended for various types of research and well testing to thoroughly investigate this alternative energy source. This volume describes the following studies: Design well program; LaFourche Crossing; MG-T/DOE Amoco Fee No. 1 (Sweet Lake); Environmental monitoring at Sweet Lake; Air quality; Water quality; Microseismic monitoring; Subsidence; Dow/DOE L.R. Sweezy No. 1 well; Reservoir testing; Environmental monitoring at Parcperdue; Air monitoring; Water runoff; Groundwater; Microseismic events; Subsidence; Environmental consideration at site; Gladys McCall No. 1 well; Test results of Gladys McCall; Hydrocarbons in production gas and brine; Environmental monitoring at the Gladys McCall site; Pleasant Bayou No. 2 well; Pleasant Bayou hybrid power system; Environmental monitoring at Pleasant Bayou; and Plug abandonment and well site restoration of three geopressured-geothermal test sites. 197 figs., 64 tabs.

  20. A Cultural Resources Survey of the E. H. Godwin Construction Site, Shelby County, Tennessee (Southwest Memphis Quadrangle)

    Science.gov (United States)

    1990-08-01

    and beech prevailed along the West Tennessee loess bluffs. Two mastodons ( Mammut americanum) have been excavated and dated from Shelby County...elsewhere in the New World, there is evidence that Pleistocene megafauna, particularly mastodon ( Mammut americanum) and mammoth (Mammuthus spp.), were

  1. Fit 2-B FATHERS.

    Science.gov (United States)

    Maiorano, Joseph J.

    2001-01-01

    Fit 2-B FATHERS is a parenting-skills education program for incarcerated adult males. The goals of this program are for participants to have reduced recidivism rates and a reduced risk of their children acquiring criminal records. These goals are accomplished by helping participants become physically, practically, and socially fit for the demands…

  2. Interferon Alfa-2b Injection

    Science.gov (United States)

    Interferon alfa-2b injection is used to treat a number of conditions.Interferon alfa-2b injection is used alone or in ... Hodgkin's lymphoma (NHL; a slow-growing blood cancer). Interferon alfa-2b is in a class of medications ...

  3. Investigation of Class 2b Trucks

    Energy Technology Data Exchange (ETDEWEB)

    Davis, S.C.

    2002-04-03

    The popularity of trucks in the class 2 category--that is, those with a 6,000 to 10,000 pounds (lbs) gross vehicle weight rating (GVWR)--has increased since the late 1970s/early 1980s. The purpose of this research is to identify and examine vehicles in the upper portion of the class 2 weight range (designated as vehicle class 2b) and to assess their impact. Vehicles in class 2b (8,500-10,000 lbs GVWR) include pickup trucks, sport utility vehicles (SUVs), and large vans (i.e., not minivans). Oak Ridge National Laboratory researched each individual truck model to determine which models were class 2b trucks and arrived at four methodologies to derive sales volumes. Two methods--one for calendar year and one for model year sales--were recommended for producing believable and reliable results. The study indicates that 521,000 class 2b trucks were sold in calendar year 1999--6.4% of sales of all trucks under 10,000 lbs. Eighty-two percent of class 2b trucks sold in 1999 were pickups; one third of class 2b trucks sold in 1999 were diesel. There were 5.8 million class 2b trucks on the road in 2000, which amounts to 7.8% of all trucks under 10,000 lbs. Twenty-four percent of the class 2b truck population is diesel. Estimates show that class 2b trucks account for 8% of annual miles traveled by trucks under 10,000 lbs and 9% of fuel use. Data on class 2b trucks are scarce. As the Tier 2 standards, which apply to passenger vehicles in the 8,500-10,000 lb GVWR category, become effective, additional data on class 2b trucks may become available--not only emissions data, but data in all areas. At the moment, distinguishing class 2b trucks from class 2 trucks in general is a substantial task requiring data on an individual model level.

  4. Numerical analysis of stiffened shells of revolution. Volume 3: Users' manual for STARS-2B, 2V, shell theory automated for rotational structures, 2 (buckling, vibrations), digital computer programs

    Science.gov (United States)

    Svalbonas, V.

    1973-01-01

    The User's manual for the shell theory automated for rotational structures (STARS) 2B and 2V (buckling, vibrations) is presented. Several features of the program are: (1) arbitrary branching of the shell meridians, (2) arbitrary boundary conditions, (3) minimum input requirements to describe a complex, practical shell of revolution structure, and (4) accurate analysis capability using a minimum number of degrees of freedom.

  5. Marketing Optimization for B2B Market

    OpenAIRE

    Kaynova Tatyana V.

    2012-01-01

    The article presents market definition B2B, the necessity to optimize marketing B2B market, provides a system for B2B-marketing and developed stages of its formation. On this basis it was identified key factors of customer loyalty and are the stages of development of loyalty programs for customers market B2B.

  6. Evaluation of effects of groundwater withdrawals at the proposed Allen combined-cycle combustion turbine plant, Shelby County, Tennessee

    Science.gov (United States)

    Haugh, Connor J.

    2016-08-10

    The Mississippi Embayment Regional Aquifer Study groundwater-flow model was used to simulate the potential effects of future groundwater withdrawals at the proposed Allen combined-cycle combustion turbine plant in Shelby County, Tennessee. The scenario used in the simulation consisted of a 30-year average withdrawal period followed by a 30-day maximum withdrawal period. Effects of withdrawals at the Allen plant site on the Mississippi embayment aquifer system were evaluated by comparing the difference in simulated water levels in the aquifers at the end of the 30-year average withdrawal period and at the end of the scenario to a base case without the Allen combined-cycle combustion turbine plant withdrawals. Simulated potentiometric surface declines in the Memphis aquifer at the Allen plant site were about 7 feet at the end of the 30-year average withdrawal period and 11 feet at the end of the scenario. The affected area of the Memphis aquifer at the Allen plant site as delineated by the 4-foot potentiometric surface-decline contour was 2,590 acres at the end of the 30-year average withdrawal period and 11,380 acres at the end of the scenario. Simulated declines in the underlying Fort Pillow aquifer and overlying shallow aquifer were both less than 1 foot at the end of the 30-year average withdrawal period and the end of the scenario.

  7. Locating suitable habitats for West Nile Virus-infected mosquitoes through association of environmental characteristics with infected mosquito locations: a case study in Shelby County, Tennessee

    Directory of Open Access Journals (Sweden)

    Bialkowska-Jelinska Elzbieta

    2008-03-01

    Full Text Available Abstract Background Since its first detection in 2001, West Nile Virus (WNV poses a significant health risk for residents of Shelby County in Tennessee. This situation forced public health officials to adopt efficient methods for monitoring disease spread and predicting future outbreaks. Analyses that use environmental variables to find suitable habitats for WNV-infected mosquitoes have the potential to support these efforts. Using the Mahalanobis Distance statistic, we identified areas of Shelby County that are ecologically most suitable for sustaining WNV, based on similarity of environmental characteristics to areas where WNV was found. The environmental characteristics in this study were based on Geographic Information Systems (GIS data, such as elevation, slope, land use, vegetation density, temperature, and precipitation. Results Our analyses produced maps of likely habitats of WNV-infected mosquitoes for each week of August 2004, revealing the areas that are ecologically most suitable for sustaining WNV within the core of the Memphis urban area. By comparing neighbourhood social characteristics to the environmental factors that contribute to WNV infection, potential social drivers of WNV transmission were revealed in Shelby County. Results show that human population characteristics and housing conditions such as a high percentage of black population, low income, high rental occupation, old structures, and vacant housing are associated with the focal area of WNV identified for each week of the study period. Conclusion We demonstrated that use of the Mahalanobis Distance statistic as a similarity index to assess environmental characteristics is a potential raster-based approach to identify areas ecologically most suitable for sustaining the virus. This approach was also useful to monitor changes over time for likely locations of infected mosquito habitats. This technique is very helpful for authorities when making decisions related to an

  8. Implication of human UGT2B7, 2B15 and 2B17 in 19-norandrosterone metabolism

    Directory of Open Access Journals (Sweden)

    Emmanuel eStrahm

    2013-06-01

    Full Text Available Nandrolone (19-nortestosterone is an anabolic androgenic steroid commonly abused for doping purposes. Nandrolone is mainly metabolized in the liver into 19-norandrosterone prior to glucuronidation and excretion through urine over an extended period of time. Several UGTs (i.e. UGT2B7, UGT2B15 and UGT2B17 are thought to be the major enzymes responsible for conjugation of androgens in human. An in-vitro study using recombinant enzymes expressed in insect cells showed that UGT1A4 and UGT2B7 are the two main enzymes responsible of 19-norandrosterone glucuronidation. However, the identity of the enzyme involved in nandrolone metabolism in vivo together with their relative contribution and regulation remain unknown.Inhibition assays using human liver microsomes incubated with 19-norandrosterone and selective inhibitors confirmed that UGT2B7 and UGT2B15 are involved in 19-norandrosterone glucuronidation, since the presence of the specific UGT2B7 and UGT2B15 inhibitors gemfibrosil and valproic acid inhibited the 19-norandrosterone glucuronidation by 35 and 45 %, respectively. Human liver microsomes were genotyped for UGT2B15 D85Y, UGT2B7 H268Y and the UGT2B17 deletion polymorphism. The glucuronidation activity on 19 norandrosterone was significantly higher in UGT2B15 DD than in the other UGT2B15 genotypes (p<0.05. Moreover, human liver cancer HepG2 cells were exposed to androgens to determine if the transcriptional activity of the genes of interest was affected. Only UGT2B7 mRNA expression was significantly increased (1.8-folds after incubation with nandrolone decanoate.These results show that the UGT2B7 and UGT2B15 are involved in 19-norandrosterone glucuronidation and that the UGT2B15 polymorphism (D85Y is the only UGT genetic variation that influences the glucuronidation activity. This could partly explain the inter-individual variation in 19 norandrosterone excretion.

  9. Implication of human UGT2B7, 2B15 and 2B17 in 19-norandrosterone metabolism

    OpenAIRE

    Emmanuel eStrahm; Ulf eSjöberg; Mats eGarle; Anders eRane; Lena eEkström

    2013-01-01

    Nandrolone (19-nortestosterone) is an anabolic androgenic steroid commonly abused for doping purposes. Nandrolone is mainly metabolized in the liver into 19-norandrosterone prior to glucuronidation and excretion through urine over an extended period of time. Several UGTs (i.e. UGT2B7, UGT2B15 and UGT2B17) are thought to be the major enzymes responsible for conjugation of androgens in human. An in-vitro study using recombinant enzymes expressed in insect cells showed that UGT1A4 and UGT2B7 are...

  10. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

    DEFF Research Database (Denmark)

    Clayton, Emma L; Mancuso, Renzo; Nielsen, Troels Tolstrup

    2017-01-01

    Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD...

  11. B2B Pioneer A Millionaire Maker

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China should soon see its largest group of instant millionaires after Jack Ma,Chief Executive Officer and Chairman of Alibaba Group,announced on July 27 that the China’s preeminent e-commerce company has initiated the listing of its B2B unit alibaba.com

  12. 2000 Johnston Site 2B-P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 2B-P was established at Johnston Atoll by Dr. James Maragos, U.S. Fish & Wildlife Service, on June 30, 2000. With a start point (meter 0) at...

  13. WTS-2 b: Too close for comfort?

    Directory of Open Access Journals (Sweden)

    Kovács G.

    2013-04-01

    Full Text Available We report the discovery of WTS-2 b, a typical hot Jupiter in an unusually close 1.02-day orbit to a K-dwarf star. This is the second planet to be discovered in the infrared light curves of the WFCAM Transit Survey (WTS and is only one-and-a-half times the separation from its host star at which is would be destroyed by Roche lobe overflow. The predicted remaining lifetime of the planet is just 38 Myrs, assuming a tidal dissipation quality factor of Q'* = 106. The magnitude of Q'* is largely unconstrained by observations, thus WTS-2 b provides a useful calibration point for theories describing how frictional processes within a host star affect the tidal orbital evolution of its companion giant planets. It is expected that stars with large convective envelopes are more efficient at dissipating the orbital energy of the planet, and WTS-2 b provides an observational constraint in the sparsely populated K-dwarf regime. In addition, despite its relatively faint magnitude, the favourable size ratio of the WTS-2 star-planet system and the predicted hot equilibrium temperature of the planet will make it possible to characterise the planet's atmosphere via secondary eclipse measurements using existing ground-based instrumentation.

  14. To be or not B2B?

    CERN Document Server

    Symons, L J

    2001-01-01

    La question du commerce électronique interentreprises par le web (Business to Business, B2B) est posée actuellement par les grands groupes industriels impliqués dans le commerce mondial. Les prévisions sont imposantes, le B2B atteindra le C.A. de 3000 milliards de dollars en 2003. Les conditions d'accès, la façon de procéder des deux organisateurs (ARIBA et COMMERCE ONE) des plus grandes places de marchés actuelles, sont décrites. La base de l'énorme pyramide est le catalogue électronique multilingue UNSPSC (United Nations Standard Products and Services Classification) et l'organisation ECCMA (Electronic Commerce Code Management Association) qui gère le développement des UNSPSC codes en 8 langues. Dans ce contexte, l'auteur (re)-déclare qu'un des efforts principaux à fournir par le CERN est la création de son propre catalogue électronique. Dans la Division ST, une aide partielle à ce vaste programme pourrait être apportée par la normalisation des codes et désignations des pièces de maint...

  15. What Happened with Spectrometer Magnet 2B

    Energy Technology Data Exchange (ETDEWEB)

    Green, Michael A

    2010-05-27

    The spectrometer solenoid is supposed to be the first magnets installed in MICE [1]-[4]. This report described what happened during the test of the MICE spectrometer solenoid 2B. First, the report describes the temperatures in the magnet, the cooler top plate and the shield during the run where the magnet quenched at 258 A. During this quench, a lead between the bottom of the HTS leads and the diode bank burned out causing the magnet to quench. Second, three methods for measuring the net heat flow into the cold mass are described. Third, there is a discussion of possible resistive heating in the HTS leads between liquid helium temperature and the copper plate, which is at about 50 K. Fourth, there is a discussion of the measured first stage heat loads in the magnet, when there is no current in the magnet. The first stage heat load calculations are based on knowing the first stage temperatures of the three two-stage pulse tube coolers and the single stage GM cooler. Fifth, the estimated heat load to the first stage when the magnet has current in it is discussed. Sixth, there is a comparison of the stage 1 heat loads in magnet 1A [5], magnet 2A [6], and magnet 2B [7]. Finally there is a discussion of recommended changes for improving the spectrometer solenoids so that the coolers can keep them cold.

  16. ONLINE ACQUISITIONS IN B2B MODEL

    Directory of Open Access Journals (Sweden)

    Constantin SASU

    2016-12-01

    Full Text Available Within the present paper, we propose to review some of the main aspects documented by the academic research so far with regard to the online purchasing behaviour in the B2B online environment (more specifically, in the case of the small and medium-sized companies. Preliminary conclusions reveal that, at least in the case studies, the dominant feature is that the geographic delimitation creates a potential obstacle when it comes to applying a general principle governing the small and medium-sized enterprises. Despite this, we consider that some theoretical elements can be acknowledged, elements from which future research can start to develop theories and hypothesis aimed at better explaining the phenomenon. Furthermore, the fact that the studies are rarely involving the same sector, makes it impossible to generalise the process.

  17. TRUST IN B2B E-MARKETPLACES

    Directory of Open Access Journals (Sweden)

    SEBASTIAN KOT

    2011-01-01

    Full Text Available The paper presents background of B2B exchanges and review of their forms and functionalities. The benefits and fails reasons are noticed. European enterprises interest in B2B trade is next aspect of consideration. Finally, the trust barriers of B2B exchanges are presented.

  18. 7 CFR 301.80-2b - Exempted articles. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit...

  19. 7 CFR 301.85-2b - Exempted articles. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  20. Genetics Home Reference: CHMP2B-related frontotemporal dementia

    Science.gov (United States)

    ... Conditions CHMP2B-related frontotemporal dementia CHMP2B-related frontotemporal dementia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description CHMP2B -related frontotemporal dementia is a progressive brain disorder that affects personality, ...

  1. Analysis list: Gtf2b [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gtf2b Blood,Cardiovascular,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2b.1.tsv htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2b.5.tsv http://dbarchive.bio...sciencedbc.jp/kyushu-u/mm9/target/Gtf2b.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Blood.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Cardiovascular.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Liver.tsv http://dbarchive.biosciencedbc.jp/kyu

  2. PTK2b function during fertilization of the mouse oocyte

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Jinping [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); McGinnis, Lynda K. [Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Carlton, Carol [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Beggs, Hilary E. [Department of Ophthalmology, University of California, San Francisco, CA (United States); Kinsey, William H., E-mail: wkinsey@kumc.edu [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2014-08-01

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.

  3. Rapid modulation of the organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) function by protein kinase C-mediated internalization.

    Science.gov (United States)

    Köck, Kathleen; Koenen, Anna; Giese, Bernd; Fraunholz, Martin; May, Karen; Siegmund, Werner; Hammer, Elke; Völker, Uwe; Jedlitschky, Gabriele; Kroemer, Heyo K; Grube, Markus

    2010-04-09

    Members of the organic anion transporting polypeptide (OATP) family are involved in various pharmacological, pathophysiological, and physiological processes, such as hepatic drug uptake, progress of cancer, or transport of hormones. Although variability in expression and function of OATPs has been investigated in detail, data concerning regulation are rather limited. Here, we report a novel mechanism for rapid regulation of OATP2B1 mediated by protein kinase C (PKC) resulting in significant changes of transport activity. PKC activation by the phorbol ester (phorbol 12-myristate 13-acetate, PMA) resulted in increased phosphorylation of OATP2B1 as well as reduced OATP2B1 transport activity with a decrease in V(max) of E(1)S uptake (288 +/- 21 (control) versus 165 +/- 16 pmol/min/mg of protein (PMA)). This effect was sensitive to the PKC inhibitor bisindolylmaleimide I (BIM-I). Confocal microscopy, fluorescence-based internalization assay, and live-cell imaging using green fluorescent protein-tagged OATP2B1 revealed that transport inhibition was due to internalization of the transporter. Furthermore, colocalization with LAMP-2 and chloroquine-sensitive degradation of OATP2B1 suggest that the internalized protein is targeted to a lysosomal degradation pathway. With regard to the underlying mechanism inhibition of caveolin/lipid raft-mediated endocytosis failed to prevent OATP2B1 internalization, whereas inhibition of clathrin-mediated processes blocked OATP2B1 sequestration. However, small interfering RNA-mediated clathrin knock-down affected general trafficking of OATP2B1 and resulted in intracellular accumulation in the absence of PMA. In conclusion, our data demonstrate that OATP2B1 function is regulated by PKC-mediated, clathrin-dependent internalization and followed by lysosomal degradation. Furthermore, internalization could be shown in an ex vivo placenta perfusion. Our findings represent a new, rapid mechanism in regulation of human OATPs.

  4. Haplotypes frequencies of CYP2B6 in Malaysia

    Directory of Open Access Journals (Sweden)

    N Musa

    2012-01-01

    Full Text Available Background: Drugs with complex pharmacology are used in the management of drug use disorder (DUD and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral. Aims: Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia. Settings and Design: The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals. Materials and Methods: For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6FNx0110, CYP2B6FNx012, CYP2B6FNx0117, CYP2B6FNx0111, CYP2B6FNx018, CYP2B6FNx0114, CYP2B6FNx019, CYP2B6FNx014, CYP2B6FNx016, CYP2B6FNx0127, and CYP2B6FNx0120 were determined using multiplex nested allele-specific PCR. Statistical Analysis: Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test. Results: CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6FNx016 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another ′reduced activity′, CYP2B6FNx012 allele, was found at much lower percentages in the groups. Conclusions: The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.

  5. Haplotypes frequencies of CYP2B6 in Malaysia.

    Science.gov (United States)

    Musa, N; Zulkafli, M I; Talib, N; Mohamad, N; Fauzi, H; Ismail, R

    2012-01-01

    Drugs with complex pharmacology are used in the management of drug use disorder (DUD) and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral. Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia. The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals. For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT) Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6*10, CYP2B6*2, CYP2B6*17, CYP2B6*11, CYP2B6*8, CYP2B6*14, CYP2B6*9, CYP2B6*4, CYP2B6*6, CYP2B6*27, and CYP2B6*20 were determined using multiplex nested allele-specific PCR. Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test. CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6*6 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another 'reduced activity', CYP2B6*2 allele, was found at much lower percentages in the groups. The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.

  6. Analysis list: GTF2B [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available GTF2B Blood,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/GT...F2B.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/GTF2B.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/GTF2B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/GTF2B.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/GTF2B.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  7. Harnessing marketing automation for B2B content marketing

    OpenAIRE

    Järvinen, Joel; Taiminen, Heini

    2016-01-01

    The growing importance of the Internet to B2B customer purchasing decisions has motivated B2B sellers to create digital content that leads potential buyers to interact with their company. This trend has engendered a new paradigm referred to as ‘content marketing.’ This study investigates the organizational processes for developing valuable and timely content to meet customer needs and for integrating content marketing with B2B selling processes. The results of this single case study demonstra...

  8. Scientific core hole Valles caldera No. 2b (VC-2b), New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Garner, J.N.; Hulen, J.B.; Lysne, P.; Jacobson, R.; Goff, F.; Nielson, D.L.; Pisto, L.; Criswell, C.W.; Gribble, R. (Los Alamos National Lab., NM (USA); Utah Univ. Research Inst., Salt Lake City, UT (USA); Sandia National Labs., Albuquerque, NM (USA); Los Alamos National Lab., NM (USA); Utah Univ. Research Inst., Salt Lake City, UT (USA); Tonto Drilling Services, Inc., Salt Lake City, UT (USA); Los Alamo

    1989-01-01

    Research core hole was continuously cored to 1.762 km on the western flank of the caldera's resurgent dome in 1988. Bottom hole temperature is about 295{degree}C within Precambrian (1.5 Ga) quartz monzonite, deep within the liquid-dominated portions of the Sulphur Springs hydrothermal system. VC-2b may be the deepest, hottest, continuously cored hole in North America. Core recovery was 99.2%. The only major drilling problems encountered were when temperatures at the bit exceeded 225{degree}C below depths of about 1000 m. The result of these conditions was loss of viscosity and/or lubricity in the mud, apparently caused by breakdown of the high temperature polymers. Lithologies in caldera-fill indicate the drill site may be proximal to ignimbrite vents and that an intracaldera lake with temperatures approaching boiling formed soon after the caldera itself. Structural correlations between VC-2b and the 528-m-deep companion hole VC-2a indicate the earlier Toledo caldera (1.45 Ma; Otowi Member tuffs) and even older Lower Tuffs caldera experienced no structural resurgence similar to the 1.12 million year old Valles caldera. The hydrothermal system penetrated by these bores, consists of a shallow vapor-rich cap, which has evolved from an earlier 200{degree}C liquid-dominated system, overlying stacked, liquid-dominated zones up to about 300{degree}C. Geochemistry of mud returns collected during drilling suggests chloride-rich geothermal fluids were entering the bore and mixing with the drilling fluids in the fractured lower Paleozoic and Precambrian sections. 23 refs., 5 figs., 1 tab.

  9. RAZVOJ B2B PORTALA ZA POTREBE ELEKTRONSKEGA POSLOVANJA

    OpenAIRE

    Slanič, Matej

    2011-01-01

    V diplomski nalogi opredelimo vlogo B2B portalov in pomen elektronskega poslovanja. B2B portale smo razvrstili glede na različne kriterije in predstavili različne modele trgovanja na njih. Velik del pozornosti smo posvetili tudi strateškemu načrtovanju B2B poslovanja in vključevanju podjetij na B2B portale, dotaknili pa smo se tudi vizije elektronskega poslovanja. Osrednji del naloge obsega predstavitev gradnje specifičnega portala Bbuines.com ter z njo povezane oblikovne in tehnološke rešitv...

  10. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

    Isaacs, A M; Johannsen, P; Holm, I;

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient. ...... features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease....

  11. Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

    DEFF Research Database (Denmark)

    Rohrer, Jonathan D; Ahsan, R Laila; Isaacs, Adrian M;

    2009-01-01

    BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no ......BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease....... There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients. METHODS: Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic...... mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups. RESULTS: We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B...

  12. Advanced complex analysis a comprehensive course in analysis, part 2b

    CERN Document Server

    Simon, Barry

    2015-01-01

    A Comprehensive Course in Analysis by Poincaré Prize winner Barry Simon is a five-volume set that can serve as a graduate-level analysis textbook with a lot of additional bonus information, including hundreds of problems and numerous notes that extend the text and provide important historical background. Depth and breadth of exposition make this set a valuable reference source for almost all areas of classical analysis. Part 2B provides a comprehensive look at a number of subjects of complex analysis not included in Part 2A. Presented in this volume are the theory of conformal metrics (includ

  13. Building Customized University-to-Business (U2B) Partnerships

    Science.gov (United States)

    Irvine, George; Verma, Lisa

    2013-01-01

    Continuing education (CE) units throughout the United States have successfully built University-to-Business (U2B) partnerships to provide greater value to their community partners and to increase revenue for the university. Our experience in building U2B partnerships and feedback from our partners--businesses, corporations, state agencies, and…

  14. Genetic and bibliographic information: HTR2B [GenLibi

    Lifescience Database Archive (English)

    Full Text Available HTR2B 5-hydroxytryptamine (serotonin) receptor 2B human alcoholism (MeSH) Disorders... of Environmental Origin (C21) > Substance-Related Disorders (C21.739) > Alcohol-Related Disorders (C21.739.100) > Alcoholism (C21.739.100.250) 01A0634580 ...

  15. B2B myynnin johtaminen ravintola-alalla

    OpenAIRE

    Pajari, Katja

    2014-01-01

    Tämän opinnäytetyön tavoitteena oli selvittää, miten ravintola-alan yrityksissä johdetaan B2B myyntiä. Tarkoituksena oli kartoittaa, miten yrityksissä panostetaan B2B myyntiin ja sen johtamiseen sekä millä tavoin yritysmyyntiä johdetaan. Tutkimus pohjautuu opinnäytetyön tietoperustaan, jossa käsitellään B2B myyntiprosessia ja myynnin johtamista. Työssä käsitellään B2B myyntiä ja selvitetään myyntiprosessin eri vaiheita. Aihe on rajattu koskemaan nimenomaan johtamisen näkökulmaa B2B myynni...

  16. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

    Isaacs, A M; Johannsen, P; Holm, I

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient....... These mutations lead to C-terminal truncations of the CHMP2B protein and we will review recent advances in our understanding of the molecular effects of these mutant truncated proteins on vesicular fusion events within the endosome-lysosome and autophagy degradation pathways. We will also review the clinical...... features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease....

  17. B2B virksomheders brug af sociale medier

    OpenAIRE

    Persdatter Gotfredsen, Karoline

    2016-01-01

    Purpose: The aim of this master thesis is to explore how B2B firms perceive their own usage of social media to establish and strengthen successful relational exchanges. Approach: In-depth interviews were carried out with three key informants responsible for social media marketing at large B2B firms. The findings from the three interviews were then analysed case-by-case and finally a cross case analysis was conducted. Findings: In relation to the market B2B firms mainly see social media...

  18. Rf2a and rf2b transcription factors

    Science.gov (United States)

    Beachy, Roger N.; Petruccelli, Silvana; Dai, Shunhong

    2007-10-02

    A method of activating the rice tungro bacilliform virus (RTBV) promoter in vivo is disclosed. The RTBV promoter is activated by exposure to at least one protein selected from the group consisting of Rf2a and Rf2b.

  19. Secretion of human interferon alpha 2b by Streptomyces lividans.

    Science.gov (United States)

    Pimienta, E; Fando, R; Sánchez, J C; Vallin, C

    2002-02-01

    Biologically active human interferon alpha 2b (HuIFNalpha-2b) was secreted into the culture medium by Streptomyces lividans transformed with recombinant plasmids coding for HuIFNalpha-2b fused to the Streptomyces exfoliatus M11 lipase A signal sequence. Levels were low, 15 or 100 ng/ml, depending on the plasmid used. Neither processed nor unprocessed HuIFNalpha-2b was detected in cell lysates of the transformants secreting the recombinant product. However, the secreted recombinant product was found to partially degrade when cultures reached the stationary phase by the action of an, as yet, unidentified mycelium-associated factor. Experimental evidence suggests that the degrading factor is related to mycelium-associated proteolytic activity.

  20. Study on pharmacodynamics of recombinant interferon α-2b suppository

    Institute of Scientific and Technical Information of China (English)

    LIU Miao; LIU Zheng; SUN Liang

    2008-01-01

    Objective To investigate the antiviral activity of recombinant interferona-2b suppository (IFNα-2b) in vivo and in vitro. Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control. The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established, treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU, using IFNα-2b injection 180000 IU·kg-1 as controls. Score the pathological changes of appearance and skin, the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment. Results The TD50 of IFN α-2b and yingtelong for Vero cells was ( 100)μg·mL-1 and ( 100000) IU·mL-1, respectively. The IC50 of IFNα-2b and yingtelong and axiluowei for Herpes virus type 1 was (0.29±0.08)μg·mL-1 and (185.0±28.8) IU·mL-1 and (0.19± 0.03)μg·mL-1, respectively. The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group. Among these concentrations, the IFNα-2b suppository of 540000 IU·kg-1 group. Showed highest anti-viral activity. The virus activity in vaginal secretion of treated group was lower than that of untreated group too (P<0.01 or P<0.05). Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion. At the same dosage, The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection , the resuits showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection. Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.

  1. Branding of electricity in B2B markets

    OpenAIRE

    Rolanda Simenaite 1986

    2013-01-01

    Branding has gained an important role in the B2B (business-to-business) market. Liberation of the energy markets in recent years has increased competition and branding could create a competitive advantage. This thesis analyzes the branding of electricity in a business-to-business context. In depth, this thesis explores the supplier of electricity brand importance for business customers in both Icelandic and Lithuanian B2B markets. The focus of the thesis is to research how much brands matter ...

  2. Expression of zebrafish nos2b surrounds oral cavity.

    Science.gov (United States)

    Poon, Kar-Lai; Richardson, Michael; Korzh, Vladimir

    2008-06-01

    Inducible nitric oxide synthase (NOS2) catalyzes the production of nitric oxide (NO), and is one of the factors establishing innate immunity. In zebrafish, Nos2 is represented by nos2a and nos2b. Here, we report the cloning and expression pattern of the zebrafish nos2b gene, which does not seem to participate in induced immune response. nos2b was mapped to zebrafish linkage group 15. The spatial and temporal expression pattern of nos2b in embryonic zebrafish was analyzed by whole-mount in situ hybridization. nos2b is expressed constitutively in two primordia located along the ventral midline. The first group of cells contributes to the neurohypophysis. Initially at the level of the ventral hindbrain, the second group of cells migrates closely with the thyroid primordium to its final position at the basihyal by 3 dpf. Thus, the analysis of expression pattern of nos2b reveals complex morphogenetic movements resulting in its expression surrounding the oral cavity.

  3. PTK2b function during fertilization of the mouse oocyte.

    Science.gov (United States)

    Luo, Jinping; McGinnis, Lynda K; Carlton, Carol; Beggs, Hilary E; Kinsey, William H

    2014-08-01

    Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development. Published by Elsevier Inc.

  4. HYDRAULICS, SHELBY COUNTY, TN, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Recent developments in digital terrain and geospatial database management technology make it possible to protect this investment for existing and future projects to...

  5. BASEMAP, SHELBY COUNTY, IOWA, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — FEMA Framework Basemap datasets comprise six of the seven FGDC themes of geospatial data that are used by most GIS applications (Note: the seventh framework theme,...

  6. FLOODPLAIN, SHELBY COUNTY, ALABAMA USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Floodplain Mapping/Redelineation study deliverables depict and quantify the flood risks for the study area. The primary risk classifications used are the...

  7. FLOODPLAIN, SHELBY COUNTY, IOWA, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Floodplain Mapping/Redelineation study deliverables depict and quantify the flood risks for the study area. The primary risk classifications used are the...

  8. TERRAIN, SHELBY COUNTY, ALABAMA USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Terrain data, as defined in FEMA Guidelines and Specifications, Appendix N: Data Capture Standards, describes the digital topographic data that was used to create...

  9. HYDROLOGY, SHELBY COUNTY, ALABAMA USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydrology data include spatial datasets and data tables necessary for documenting the hydrologic procedures for estimating flood discharges for a flood insurance...

  10. SURVEY, SHELBY COUNTY, TN, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Survey data includes spatial datasets and data tables necessary to digitally represent data collected in the survey phase of the study. (Source: FEMA Guidelines and...

  11. HYDRAULICS, SHELBY COUNTY, TN, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Recent developments in digital terrain and geospatial database management technology make it possible to protect this investment for existing and future projects to...

  12. Pharmacogenetics of Cytochrome P450 2B6 (CYP2B6: Advances on Polymorphisms, Mechanisms, and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ulrich M Zanger

    2013-03-01

    Full Text Available Cytochrome P450 2B6 (CYP2B6 belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both between individuals and within individuals, owing to nongenetic factors, genetic polymorphisms, inducibility and irreversible inhibition by many compounds. Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone. CYP2B6 is one of the most polymorphic CYP genes in humans and variants have been shown to affect transcriptional regulation, splicing, mRNA and protein expression, and catalytic activity. Some variants appear to affect several functional levels simultaneously, thus, combined in haplotypes, leading to complex interactions between substrate-dependent and -independent mechanisms. The most common functionally deficient allele is CYP2B6*6 [Q172H, K262R], which occurs at frequencies of 15 to over 60% in different populations. The allele leads to lower expression in liver due to erroneous splicing. Recent investigations suggest that the amino acid changes contribute complex substrate-dependent effects at the activity level, although data from recombinant systems used by different researchers are not well in agreement with each other. Another important variant, CYP2B6*18 [I328T], occurs predominantly in Africans (4 to 12% and does not express functional protein. A large number of uncharacterized variants are currently emerging from different ethnicities in the course of the 1000 Genomes Project. The CYP2B6 polymorphism is clinically relevant for HIV-infected patients treated with the reverse transcriptase inhibitor efavirenz, but it is increasingly being recognized for other drug substrates. This review summarizes recent advances on the functional and clinical significance of CYP2B6 and its genetic polymorphism, with particular emphasis on the comparison of kinetic data obtained with different substrates for variants expressed in different recombinant

  13. Targeted deletion of titin N2B region leads to diastolic dysfunction and cardiac atrophy.

    Science.gov (United States)

    Radke, Michael H; Peng, Jun; Wu, Yiming; McNabb, Mark; Nelson, O Lynne; Granzier, Henk; Gotthardt, Michael

    2007-02-27

    Titin is a giant protein that is in charge of the assembly and passive mechanical properties of the sarcomere. Cardiac titin contains a unique N2B region, which has been proposed to modulate elasticity of the titin filament and to be important for hypertrophy signaling and the ischemic stress response through its binding proteins FHL2 and alphaB-crystallin, respectively. To study the role of the titin N2B region in systole and diastole of the heart, we generated a knockout (KO) mouse deleting only the N2B exon 49 and leaving the remainder of the titin gene intact. The resulting mice survived to adulthood and were fertile. Although KO hearts were small, they produced normal ejection volumes because of an increased ejection fraction. FHL2 protein levels were significantly reduced in the KO mice, a finding consistent with the reduced size of KO hearts. Ultrastructural analysis revealed an increased extension of the remaining spring elements of titin (tandem Ig segments and the PEVK region), which, together with the reduced sarcomere length and increased passive tension derived from skinned cardiomyocyte experiments, translates to diastolic dysfunction as documented by echocardiography. We conclude from our work that the titin N2B region is dispensable for cardiac development and systolic properties but is important to integrate trophic and elastic functions of the heart. The N2B-KO mouse is the first titin-based model of diastolic dysfunction and, considering the high prevalence of diastolic heart failure, it could provide future mechanistic insights into the disease process.

  14. Lithium insertion in nanostructured TiO(2)(B) architectures.

    Science.gov (United States)

    Dylla, Anthony G; Henkelman, Graeme; Stevenson, Keith J

    2013-05-21

    Electric vehicles and grid storage devices have potentialto become feasible alternatives to current technology, but only if scientists can develop energy storage materials that offer high capacity and high rate capabilities. Chemists have studied anatase, rutile, brookite and TiO2(B) (bronze) in both bulk and nanostructured forms as potential Li-ion battery anodes. In most cases, the specific capacity and rate of lithiation and delithiation increases as the materials are nanostructured. Scientists have explained these enhancements in terms of higher surface areas, shorter Li(+) diffusion paths and different surface energies for nanostructured materials allowing for more facile lithiation and delithiation. Of the most studied polymorphs, nanostructured TiO2(B) has the highest capacity with promising high rate capabilities. TiO2(B) is able to accommodate 1 Li(+) per Ti, giving a capacity of 335 mAh/g for nanotubular and nanoparticulate TiO2(B). The TiO2(B) polymorph, discovered in 1980 by Marchand and co-workers, has been the focus of many recent studies regarding high power and high capacity anode materials with potential applications for electric vehicles and grid storage. This is due to the material's stability over multiple cycles, safer lithiation potential relative to graphite, reasonable capacity, high rate capability, nontoxicity, and low cost (Bruce, P. G.; Scrosati, B.; Tarascon, J.-M. Nanomaterials for Rechargeable Lithium Batteries. Angew. Chem., Int. Ed.2008, 47, 2930-2946). One of the most interesting properties of TiO2(B) is that both bulk and nanostructured forms lithiate and delithiate through a surface redox or pseudocapacitive charging mechanism, giving rise to stable high rate charge/discharge capabilities in the case of nanostructured TiO2(B). When other polymorphs of TiO2 are nanostructured, they still mainly intercalate lithium through a bulk diffusion-controlled mechanism. TiO2(B) has a unique open crystal structure and low energy Li

  15. Cytochrome P450 2B (CYP2B)-mediated activation of methyl-parathion in rat brain extracts.

    Science.gov (United States)

    Albores, A; Ortega-Mantilla, G; Sierra-Santoyo, A; Cebrián, M E; Muñoz-Sánchez, J L; Calderón-Salinas, J V; Manno, M

    2001-10-15

    The role of cytochrome P450 (CYP) and the CYP isoform involved in the activation of the widely used pesticide methyl-parathion (MePA) were investigated in rat brain extracts by measuring the effect of different CYP inhibitors on acetylcholinesterase (AChE) inhibition by MePA. Brain extracts provide a useful tool to study the activation mechanisms of organophosphorus compounds (OP) since they contain both the activating enzyme(s) and the molecular target for OP toxicity. As expected, in incubations of rat brain extract supplemented with NADPH, AChE activity was non-competitively inhibited by the presence of MePA, indicating that MePA was activated to its reactive metabolite methyl-paraoxon (MePO). Indeed, Vmax(app) decreased from 13.4 to 8.7 micromol thionitrobenzoic acid (TNB)/min per mg protein. MePA activation by rat brain extracts, as measured by the AChE inhibition produced by the presence of the pesticide in the incubation, was fully prevented by previously bubbling the incubation mix with CO, by the presence of monoclonal anti-rat CYP2B1/2B2 antibodies and by the addition of phenobarbital (PB), a CYP2B substrate. Interestingly, MePA showed a greater affinity for CYP2B than PB. CYP1A1 antibodies showed no effect on MePA activation. The presence of cytochrome P450 2B (CYP2B) in the rat brain extracts was confirmed by immunoblotting. These results demonstrate indisputably the responsibility of CYP2B in MePA activation in the rat brain in vitro, suggesting that metabolic activation of OP compounds in situ might be crucial for their organ specific toxicity to the central nervous system also in vivo.

  16. Applying conceptual design to B2B sales negotiations

    DEFF Research Database (Denmark)

    Illi, Mikko; Ylirisku, Salu

    This paper addresses the challenge of perceiving B2B sales negotiation in a manner that would open up new possibilities for the improvement of the practice. B2B sales agents work under high pressure in developing relevant and appealing proposals when negotiating for a deal with a customer. The key...... problem that will be addressed is the building of understanding of a customer’s current needs and requirements, and then trying to devise an appropriate proposal to match these. The work of the sales agents in B2B sales negotiations is highly complex, as they need to understand both the modular machinery......, service, configuration and customisation of the products in their company as well as to develop an apposite understanding of the key values and characteristics of the client organisation. Based on a design-ethnographical study of real sales practice in lift truck business the paper draws parallels between...

  17. Substrate Recognition of Histone H2B by DUBm

    Science.gov (United States)

    Henderson, Elizabeth; Berndsen, Christopher; Wolberger, Cynthia

    2011-03-01

    The SAGA complex is a transcriptional coactivator that regulates gene expression in eukaryotes via histone acetylation and deubiquitination, which are crucial for transcription. Our lab is investigating the SAGA-dependent deubiquitination of histone H2B. The deubiquitinating module (DUBm) of SAGA is comprised of a ubiquitin-specific protease, Ubp8, and three other proteins. It is known that Ubp8 cleaves ubiquitin from histone H2B, however, the specific way in which the enzyme binds to the substrate remains elusive. In order to unravel this mechanism, we attempted to determine the crystal structure of the substrate binding complex. We obtained this substrate by exploiting the techniques of intein chemistry to artificially ubiquitinate a histone H2B peptide, which we then co-crystallized with DUBm. Additionally, we synthesized Ub-K63R-linked chains and Ub-K48-linked chains and co-crystallized them with DUBm.

  18. Applying conceptual design to B2B sales negotiations

    DEFF Research Database (Denmark)

    Illi, Mikko; Ylirisku, Salu

    sales agent’s work practice and collaborative conceptual design work, i.e. innovation design work. This perception provides a means to understand the value that the use of conceptual design tools could possibly provide for sales negotiation work. We also use the notion of boundary object to elaborate......This paper addresses the challenge of perceiving B2B sales negotiation in a manner that would open up new possibilities for the improvement of the practice. B2B sales agents work under high pressure in developing relevant and appealing proposals when negotiating for a deal with a customer. The key...... problem that will be addressed is the building of understanding of a customer’s current needs and requirements, and then trying to devise an appropriate proposal to match these. The work of the sales agents in B2B sales negotiations is highly complex, as they need to understand both the modular machinery...

  19. Development of New B2B Venture Corporate Brand Identity

    DEFF Research Database (Denmark)

    Törmälä, Minna; Gyrd-Jones, Richard I.

    2017-01-01

    The development and role of brand identity in new B2B ventures is not well explored despite the challenge for such organisations in establishing reputational legitimacy. Previous research defines corporate brand identity as stable and endogenous to the organisation based either on the reputational...... of interviews and archival data generated during a three-year period to examine the development of corporate brand over time. This study shows that the development of corporate brand identity and the context of the development of new B2B venture are closely intertwined processes and provides a framework...

  20. Customized E-Learning for B2B Companies

    Directory of Open Access Journals (Sweden)

    Tim Thomasma

    2014-06-01

    Full Text Available Business-to-Business (B2B companies have customers that are primarily other corporations. These companies have unique problems in workplace training. They must train their customers and their customers’ employees. A B2B company may operate with only a few dozen employees, but they may need to help thousands of customers learn how to make best use of their product or service. Discussions with industry executives suggest an ideal training solution might include a number of features that are reviewed in this paper.

  1. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

    Biemans, Wim G.; Brencic, Maja Makovec; Malshe, Avinash; Makovec Brenciv, M.

    2010-01-01

    As the body of knowledge on marketing-sales interface expands, there is a greater need to investigate the specific aspects of marketing-sales configurations in B2B firms. Using a qualitative methodology and interview data collected from over 100 sales and marketing professionals from the US, The Net

  2. Supporting B2B Business Documents in XML Web Services

    Institute of Scientific and Technical Information of China (English)

    KIM Hyoungdo

    2004-01-01

    While XML web services become recognized as a solution to business-to-business transactions, there are many problems that should be solved. For example, it is not easy to manipulate business documents of existing standards such as RosettaNet and UN/EDIFACT EDI, traditionally regarded as an important resource for managing B2B relationships. As a starting point for the complete implementation of B2B web services, this paper deals with how to support B2B business documents in XML web services. In the first phase, basic requirements for driving XML web services by business documents are introduced. As a solution, this paper presents how to express B2B business documents in WSDL, a core standard for XML web services. This kind of approach facilitates the reuse of existing business documents and enhances interoperability between implemented web services. Furthermore, it suggests how to link with other conceptual modeling frameworks such as ebXML/UMM, built on a rich heritage of electronic business experience.

  3. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

    Biemans, Wim G.; Brencic, Maja Makovec; Malshe, Avinash; Makovec Brenciv, M.

    As the body of knowledge on marketing-sales interface expands, there is a greater need to investigate the specific aspects of marketing-sales configurations in B2B firms. Using a qualitative methodology and interview data collected from over 100 sales and marketing professionals from the US, The

  4. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

    Biemans, Wim G.; Brencic, Maja Makovec; Malshe, Avinash; Makovec Brenciv, M.

    2010-01-01

    As the body of knowledge on marketing-sales interface expands, there is a greater need to investigate the specific aspects of marketing-sales configurations in B2B firms. Using a qualitative methodology and interview data collected from over 100 sales and marketing professionals from the US, The Net

  5. Mechanochemical synthesis and characterization of pure Co$_2$B nanocrystals

    Indian Academy of Sciences (India)

    MUSTAFA BARIS; TUNCAY SIMSEK; ADNAN AKKURT

    2016-08-01

    Cobalt boride (Co$_2$B) is a significant transition metal boride having a wide range of usage area due to its high oxidation, abrasion and corrosion resistance as well as its superior electrochemical, magnetic and anisotropicproperties. In this study, pure Co2B nanocrystals were synthesized with Co, B$_2$O$_3$ and Mg as starting materials via the mechanochemical synthesis (MCS) method by high-energy planetary ball mill in a hardened steel vial withhardened steel balls. All the experiments were conducted under Ar atmosphere at different rotational speeds and at 20:1–30:1–40:1 ball-to-powder ratios. Leaching of Co$_2$B $+$ MgO powder mixtures occurred after milling andpurified with acetic acid and pure Co$_2$B nanocrystals were obtained in solid form. The Co2Bs were characterized through X-ray diffraction, scanning electronmicroscopy, vibrating samplemagnetometer, Brunauer–Emmett–Tellerand specific density analyses, and effects of synthesis parameters on product properties were revealed. Surface areas of the powders synthesized at 40:1 ball-to-powder ratio at different rotational speeds were measured as 21.14,40.36 and 52.33 m$^2$ g$^{−1}$, respectively. Crystallite sizes of Co$_2$B nanocrystals were between 7.27 and 9.84 nm and their specific density varied between 7.61 and 7.78 g cm$^{−3}$. It was determined that all samples were saturated and exhibited hysteresis and ferromagnetic behaviours, and saturation magnetization was between 35 and 50 emu g$^{−1}$.

  6. GRIN2B predicts attention problems among disadvantaged children.

    Science.gov (United States)

    Riva, Valentina; Battaglia, Marco; Nobile, Maria; Cattaneo, Francesca; Lazazzera, Claudio; Mascheretti, Sara; Giorda, Roberto; Mérette, Chantal; Émond, Claudia; Maziade, Michel; Marino, Cecilia

    2015-07-01

    It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies.

  7. Morphologies of A_2B Simple Graft Copolymer Blends: Copolymer/Copolymer and Copolymer/Homopolymer Systems to Further Elucidate the Stability of Simple Graft Phase Behavior

    Science.gov (United States)

    Lee, Chin; Pochan, Darrin; Gido, Samuel P.; Pispas, Stergios; Mays, Jimmy; Tan, Nora Beck; Trevino, Samuel

    1997-03-01

    The morphological behavior of two series of binary blends of A_2B simple graft block copolymers (A is polyisoprene and B is polystyrene) was characterized via transmission electron microscopy (TEM) and small-angle neutron scattering (SANS). Binary blends of A_2B samples with other A_2B samples of similar relative volume fractions were composed to map out the volume fraction window of stability of the randomly oriented worm phase, or ROW. This novel equilibrium phase behavior was found to occur in a neat A_2B sample with a B volume fraction of 0.81. At this unique composition the single B graft chain first becomes large enough to force the two A chains to the concave side of the AB interface in the microphase separated state. Another set of binary blends of A_2B samples was composed with the respective homopolymers in order to more rigorously determine the phase boundaries relative to volume fraction of the respective microphase separated morphologies in the A_2B systems.

  8. Natural Propagation and Habitat improvement, Volume 2B, Washington, Similkameen River Habitat Inventory, 1983 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Unknown Author

    1984-04-01

    During the summer low flow period, a habitat assessment of the Similkameen, Tulameen, Ashnola and Pasayten rivers in British Columbia and Washington State was conducted between August 10 and October 10, 1983. The biophysical survey assessed 400 km (250 mi) of stream at 77 stations. Fish sampling was conducted at each station to assess the resident fish populations and standing crop. Rainbow trout populations and standing crops were found to be very low. Large populations of mountain whitefish and bridgelip suckers were present in the manstem Similkameen River below Similkameen Falls. High densities of sculpins and longnose dace were found throughout the system except for sculpins above the falls, where none were captured. Approximately 961,000 m/sup 2/ (1,150,000 yd/sup 2/) of spawnable area for steelhead trout were estimated for the entire system which could accommodate 98,000 spawners. Nearly 367,000 m/sup 2/ (439,000 yd/sup 2/) of chinook salmon spawnable area was also estimated, capable of accommodating 55,000 chinook. Rearing area for steelhead trout smolts was estimated for the whole system at 1.8 million m/sup 2/ (2.2 million yd/sup 2/). Chinook salmon smolt rearing area was estimated at 700,000 m/sup 2/ (837,000 yd/sup 2/). Rearing area was found to be a limiting factor to anadromous production in a Similkameen River system. Smolt production from the system was estimated 610,000 steelhead trout and between 1.6 million and 4.8 million chinook salmon. No water quality, temperature or flow problems for anadromous salmonids were evident from the available data and the habitat inventory. In addition to an impassable falls on the Tulameen River at river mile 32.5, only two other areas of difficult passage exist in the system, Similkameen Falls (a series of chutes) and the steep, narrow lower section of the Ashnola River. 51 references, 18 figures, 25 tables.

  9. APPROACH TO ESTIMATION OF THE MARKET VOLUME FOR COMPANIES OPERATING IN THE B2B SEGMENT

    Directory of Open Access Journals (Sweden)

    Alla B. Kochergina

    2014-01-01

    Full Text Available This article shows the approach for estimating amount of alive enterprises inRussia. The main focus is on the way of detecting an business-active companiesusing the formal signs. The author proposes some signs for indicating of thebusiness activity. The developed model allows to clarify the amount of active enterprises in stages using those signs. The author provides the approach how to applythis model for different markets.

  10. An Intensive Survey of Archaeological Resources in the Proposed Long Branch Reservoir. Volume 2B

    Science.gov (United States)

    1977-01-01

    heavy Gb - Gabbro VH - very heavy G - Granite DGb - Dolerite/Gabbro Remarks Grd - Grano -Diorite p - pecked dD - Diorite/Dolerite pk - pecked area GbD...2) Felsite 57g 57g Grano -Diorite 1 1 (2) 45g 183g 2283 Gneissic 2 1 (3) Dolerite/Gabbro 195g 197g 392g Indeterminant 1 (1) 77g 77g (57) (579 (592...Basalt 1 2 (3) 16g 86g 102g Metamorphozed 1 2 1 (4) Felsite 3g 51g 169g 223g Feloo-Diorite 1 (1) 162g 162g Grano -Diorite 2 (2) 324g 32 4g Quartz 1 1 2 (4

  11. A History of Satellite Reconnaissance. Volume 2B. SAMOS E-5 and E-6 (REDACTED)

    Science.gov (United States)

    1973-10-01

    cameras, capsules, and acces.ories wert.’ well alung toward cumpletion by December 1961. Most cost. ;end habilities had been incurred and could not be...U/NRO to SAFSP, 7 Nuv 63, 31, • el to D/NRO, 1 Apr 64, in NRO fU.a, 078l, D/NRO (B. McMillan) toSAFSP ret’r), Dt·c 63 (confirming verbal ord.rs

  12. Structured Crowdsourcing: A B2B Innovation Roadmap

    DEFF Research Database (Denmark)

    Edgeman, Rick; Engell, Toke; Jensen, Nik Grewy

    Crowdsourcing is an increasingly popular source of both ideas and funding. Crowdsourcing in a B2B context is less well understood and, as such, much of our discussion will highlight business-to-business crowdsourcing. More generally discussion will address crowdsourcing relative to innovation...... from crowd-sourcing efforts. The roadmap emphasizes on early stages in the overall innovation management activity that is related to development and specification of the task to be crowdsourced, the identification of the crowd, the creation of the environment to connect the crowdsourcer, the task...... and the crowd, motivation of the crowd, and actual activities in reaching the crowd. Managing the input from the crowd is regarded as a later stage in the overall innovation management but also as a focal point in the arguments for improving B2B crowdsourcing. In crowd selection processes this paper aims...

  13. Chemical Reactivity Perspective into the Group 2B Metals Halides.

    Science.gov (United States)

    Özen, Alimet Sema; Akdeniz, Zehra

    2016-06-30

    Chemical reactivity descriptors within the conceptual density functional theory can be used to understand the nature of the interactions between two monomers of the Group 2B metal halides. This information might be valuable in the development of adequate force law parameters for simulations in the liquid state. In this study, MX2 monomers and dimers, where M = Zn, Cd, Hg and X = F, Cl, Br, I, were investigated in terms of chemical reactivity descriptors. Relativistic effects were taken into account using the effective core potential (ECP) approach. Correlations were produced between global and local reactivity descriptors and dimerization energies. Results presented in this work represent the first systematic investigation of Group 2B metal halides in the literature from a combined point of view of both relativistic effects and chemical reactivity descriptors. Steric effects were found to be responsible for the deviation from the chemical reactivity principles. They were introduced into the chemical reactivity descriptors such as local softness.

  14. B2B Integration in Global Supply Chains

    DEFF Research Database (Denmark)

    Schubert, Petra; Legner, Christine

    2011-01-01

    The competitiveness of businesses is increasingly dependent on their electronic networks with customers, suppliers, and partners. While the strategic and operational impact of external integration and IOS adoption has been extensively studied, much less attention has been paid to the organizational...... and technical design of electronic relationships. The objective of our longitudinal research project is the development of a framework for understanding and explaining B2B integration. Drawing on existing literature and empirical cases we present a reference model (a classification scheme for B2B Integration...... and is independent of specific implementation technologies. In the next stage of the research the emerging reference model will be extended to create an assessment model for analysing the maturity level of a given company in a specific supply chain....

  15. Inbound-markkinoinnin opas pienille B2B-asiantuntijayrityksille

    OpenAIRE

    Halonen, Tuija

    2016-01-01

    Digitalisaatio on muuttanut asiakkaiden ostokäyttäytymistä, minkä vuoksi myös markkinoinnin on muututtava. Asiakaslähtöinen inbound-markkinointi on vetovoimainen vaihtoehto perinteiselle yksisuuntaiselle markkinoinnille, jonka teho on laskussa. Tämän toiminnallisen opinnäytetyön tarkoituksena oli rakentaa opas, joka auttaa pieniä suomalaisia B2B-asiantuntijayrityksiä suunnittelemaan ja toteuttamaan toimivaa ja kustannustehokasta inbound-markkinointia. Teoreettisen viitekehyksen pohjal...

  16. B2B Models for DoD Acquisition

    Science.gov (United States)

    2008-01-15

    business (B2B) e- commerce refers to transactions between businesses conducted electronically over the Internet, intranets, extranets, or private...types of electronic marketplace participation: 1) Sell-side, 2) Buy- side, 3) Exchanges, and 4) Collaborative commerce . In sell-side commerce , there...types are collectively referred to as company-centric electronic commerce , because they address a single company buying or selling needs. Exchanges

  17. CBERS-2B Monitored Forest Fires In Yunnan Province

    Institute of Scientific and Technical Information of China (English)

    Rain.L

    2008-01-01

    @@ Several forest fires hit Yunnan Province,in the southwest of China from April 6 to 9.Two disastrous fires happened near Shangri-La County,Yunnan Province.According to the requirement of the Land and Surveying Department of Yunnan Province,the China Center for Resources Satellite Data & Application (CRESDA) provided satellite monitoring images to detect the events.The processed CBERS-2B images were delivered to the related departments for decision making and disaster relief.

  18. Agent-based services for B2B electronic commerce

    Science.gov (United States)

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  19. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Science.gov (United States)

    2010-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes... + Dry Point) / 2 (b) Aromatic Hydrocarbon Solvents...

  20. Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I

    Directory of Open Access Journals (Sweden)

    Habib Philip

    2011-08-01

    Full Text Available Abstract Background Limb girdle muscular dystrophies (LGMD are inclusive of 7 autosomal dominant and 14 autosomal recessive disorders featuring progressive muscle weakness and atrophy. Studies of cardiac function have not yet been well-defined in deficiencies of dysferlin (LGMD2B and fukutin related protein (LGMD2I. In this study of patients with these two forms of limb girdle muscular dystrophy, cardiovascular magnetic resonance (CMR was used to more specifically define markers of cardiomyopathy including systolic dysfunction, myocardial fibrosis, and diastolic dysfunction. Methods Consecutive patients with genetically-proven LGMD types 2I (n = 7 and 2B (n = 9 and 8 control subjects were enrolled. All subjects underwent cardiac magnetic resonance (CMR on a standard 1.5 Tesla clinical scanner with cine imaging for left ventricular (LV volume and ejection fraction (EF measurement, vector velocity analysis of cine data to calculate myocardial strain, and late post-gadolinium enhancement imaging (LGE to assess for myocardial fibrosis. Results Sixteen LGMD patients (7 LGMD2I, 9 LGMD2B, and 8 control subjects completed CMR. All but one patient had normal LV size and systolic function; one (type 2I had severe dilated cardiomyopathy. Of 15 LGMD patients with normal systolic function, LGE imaging revealed focal myocardial fibrosis in 7 (47%. Peak systolic circumferential strain rates were similar in patients vs. controls: εendo was -23.8 ± 8.5vs. -23.9 ± 4.2%, εepi was -11.5 ± 1.7% vs. -10.1 ± 4.2% (p = NS for all. Five of 7 LGE-positive patients had grade I diastolic dysfunction [2I (n = 2, 2B (n = 3]. that was not present in any LGE-negative patients or controls. Conclusions LGMD2I and LGMD2B generally result in mild structural and functional cardiac abnormalities, though severe dilated cardiomyopathy may occur. Long-term studies are warranted to evaluate the prognostic significance of subclinical fibrosis detected by CMR in these patients.

  1. Neoplasia endocrina múltiple tipo-2b

    OpenAIRE

    Lastra, Guido; de Franco, Roberto; Rueda P., Pedro Nel; Pradilla S., Lina P.; Paz C., Óscar

    2014-01-01

    La neoplasia endocrina multiple tipo 2 comprendetres sindromes : la neoplasia endocrina múltiple2A con predisposición genética para desarrollarcarcinoma medular del tiroides,feocromocitoma e hiperplasia primaria deparatiroides. La neoplasia endocrina múltiple 2B,desorden autosómico dominante con feocromocitomay carcinoma medular del tiroides quegeneralmente se presenta a una edad más tempranay es más agresivo que la de tipo 2A, porlo que su diagnóstico precoz es crítico; estospacientes, que t...

  2. Main: 1I2B [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1I2B シロイヌナズナ Arabidopsis Arabidopsis thaliana (L.) Heynh. Udp-Sulfoquinovose Syntha...Molecule: Sulfolipid Biosynthesis Protein Sqd1; Chain: A; Engineered: Yes; Mutation: Yes Biosynthetic Protein... M.J.Theisen, S.L.Sanda, S.L.Ginell, C.Benning, R.M.Garavito M.J.Theisen, S.L.Sanda, S.L.Gin...ell, C.Benning, R.M.Garavito Characterization Of The Active Site Of Udp-Sulfoquinovose Synthase:... Formation Of The Sulfonic Acid Product In The Crystalline State To Be Published Sdr, Short-Chain Dehydrogen

  3. USING UML SCENARIOS IN B2B SYSTEMS

    Directory of Open Access Journals (Sweden)

    A. Jakimi

    2010-05-01

    Full Text Available Scenarios has become a popular technique for requirements elicitation and specification building. Since scenarios capture only partial descriptions of the system behavior, an approach for scenario composition and/or integration is needed to produce more complete specifications. The Unified Modeling Language (UML, which has become a standard notation for object-oriented modeling, provides a suitable framework for scenario acquisition using Use Case diagrams and Sequence or Collaboration diagrams. In this paper, we suggest an algorithmic and tool support for composing and integrating scenarios that are represented in form of sequence diagrams. We suggest four operators (;: sequential operator, ||: concurrent operator, ?: conditional operator and  * :iteration operator to compose a set of scenarios that describe a use case of a given system. In this paper, we suggest also to apply the scenario approach to B2B systems (Business to Business. We propose to develop B2B systems as a three activities process deriving formal specifications and code skeletons from UML scenarios. Activities of this proposed process are generally automatic and are supported by a set of developed algorithms and tools.

  4. 2b or Not 2b: Experimental Evolution of Functional Exogenous Sequences in a Plant RNA Virus

    Science.gov (United States)

    Zwart, Mark P.; Ambrós, Silvia; Carrasco, José L.; Elena, Santiago F.

    2017-01-01

    Horizontal gene transfer (HGT) is pervasive in viruses and thought to be a key mechanism in their evolution. On the other hand, strong selective constraints against increasing genome size are an impediment for HGT, rapidly purging horizontally transferred sequences and thereby potentially hindering evolutionary innovation. Here, we explore experimentally the evolutionary fate of viruses with simulated HGT events, using the plant RNA virus Tobacco etch virus (TEV), by separately introducing two functional, exogenous sequences to its genome. One of the events simulates the acquisition of a new function though HGT of a conserved AlkB domain, responsible for the repair of alkylation or methylation damage in many organisms. The other event simulates the acquisition of a sequence that duplicates an existing function, through HGT of the 2b RNA silencing suppressor from Cucumber mosaic virus. We then evolved these two viruses, tracked the maintenance of the horizontally transferred sequences over time, and for the final virus populations, sequenced their genome and measured viral fitness. We found that the AlkB domain was rapidly purged from the TEV genome, restoring fitness to wild-type levels. Conversely, the 2b gene was stably maintained and did not have a major impact on viral fitness. Moreover, we found that 2b is functional in TEV, as it provides a replicative advantage when the RNA silencing suppression domain of HC-Pro is mutated. These observations suggest a potentially interesting role for HGT of short functional sequences in ameliorating evolutionary constraints on viruses, through the duplication of functions. PMID:28137747

  5. Biodegradation of BOD and ammonia-free using bacterial consortium in aerated fixed film bioreactor (AF2B)

    Science.gov (United States)

    Prayitno, Rulianah, Sri; Saroso, Hadi; Meilany, Diah

    2017-06-01

    BOD and Ammonia-free (NH3-N) are pollutants of hospital wastewater which often exceed the quality standards. It is because biological processes in wastewater treatment plant (WWTP) have not been effective in degrading BOD and NH3-N. Therefore, a study on factors that influence the biodegradation of BOD and NH3-N by choosing the type of bacteria to improve the mechanisms of biodegradation processes is required. Bacterial consortium is a collection of several types of bacteria obtained from isolation process, which is known to be more effective than a single bacterial in degrading pollutants. On the other hand, AF2B is a type of reactor in wastewater treatment system. The AF2B contains a filter media that has a large surface area so that the biodegradation process of pollutants by microorganism can be improved. The objective of this research is to determine the effect of volume of starter and air supplies on decreasing BOD and NH3-N in hospital wastewater using bacterial consortium in the AF2B on batch process. The research was conducted in three stages: the making of the growth curve of the bacterial consortium, bacterial consortium acclimatization, and hospital wastewater treatment in the AF2B with batch process. The variables used are the volume of starter (65%, 75%, and 85% in volume) and air supplies (2.5, 5, and 7.5 L/min). Meanwhile, the materials used are hospital wastewater, bacterial consortium (Pseudomonas diminuta, Pseudomonas capica, Bacillius sp, and Nitrobacter sp), blower, and AF2B. AF2B is a plastic basin containing a filter media with a wasp-nest shape used as a medium for growing the bacterial consortium. In the process of making the growth curve, a solid form of bacterial consortium was dissolved in sterilized water, then grown in a nutrient broth (NB). Then, shaking and sampling were done at any time to determine the path growth of bacterial consortium. In the acclimatization process, bacterial isolates were grown using hospital wastewater as a

  6. Encephalomyocarditis virus viroporin 2B activates NLRP3 inflammasome.

    Directory of Open Access Journals (Sweden)

    Minako Ito

    Full Text Available Nod-like receptors (NLRs comprise a large family of intracellular pattern- recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed the inflammasomes. The NLR family, pyrin domain-containing 3 (NLRP3 is triggered by a diverse set of molecules and signals, and forms the NLRP3 inflammasome. Recent studies have indicated that both DNA and RNA viruses stimulate the NLRP3 inflammasome, leading to the secretion of interleukin 1 beta (IL-1β and IL-18 following the activation of caspase-1. We previously demonstrated that the proton-selective ion channel M2 protein of influenza virus activates the NLRP3 inflammasome. However, the precise mechanism by which NLRP3 recognizes viral infections remains to be defined. Here, we demonstrate that encephalomyocarditis virus (EMCV, a positive strand RNA virus of the family Picornaviridae, activates the NLRP3 inflammasome in mouse dendritic cells and macrophages. Although transfection with RNA from EMCV virions or EMCV-infected cells induced robust expression of type I interferons in macrophages, it failed to stimulate secretion of IL-1β. Instead, the EMCV viroporin 2B was sufficient to cause inflammasome activation in lipopolysaccharide-primed macrophages. While cells untransfected or transfected with the gene encoding the EMCV non-structural protein 2A or 2C expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells transfected with the gene encoding the EMCV 2B or influenza virus M2 protein. 2B proteins of other picornaviruses, poliovirus and enterovirus 71, also caused the NLRP3 redistribution. Elevation of the intracellular Ca(2+ level, but not mitochondrial reactive oxygen species and lysosomal cathepsin B, was important in EMCV-induced NLRP3 inflammasome activation. Chelation of extracellular Ca(2+ did not reduce virus-induced IL-1β secretion. These results indicate that EMCV activates the NLRP3 inflammasome by

  7. 20 CFR 655.22 - Obligations of H-2B employers.

    Science.gov (United States)

    2010-04-01

    ... required by law that the employer will make from the worker's paycheck. All deductions must be reasonable... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Obligations of H-2B employers. 655.22 Section... States (H-2B Workers) § 655.22 Obligations of H-2B employers. An employer seeking H-2B labor...

  8. Host choice and West Nile virus infection rates in blood-fed mosquitoes, including members of the Culex pipiens complex, from Memphis and Shelby County, Tennessee, 2002-2003.

    Science.gov (United States)

    Savage, Harry M; Aggarwal, Deepak; Apperson, Charles S; Katholi, Charles R; Gordon, Emily; Hassan, Hassan K; Anderson, Michael; Charnetzky, Dawn; McMillen, Larry; Unnasch, Emily A; Unnasch, Thomas R

    2007-01-01

    The source of bloodmeals in 2,082 blood-fed mosquitoes collected from February 2002 through December 2003 in Memphis and surrounding areas of Shelby County, Tennessee were determined. Members of the genus Culex and Anopheles quadrimaculatus predominated in the collections. Members of the Cx. pipiens complex and Cx. restuans were found to feed predominately upon avian hosts, though mammalian hosts made up a substantial proportion of the bloodmeals in these species. No significant difference was seen in the host class of bloodmeals in mosquitoes identified as Cx. pipiens pipiens, Cx. p. quinquefasciatus, or hybrids between these two taxa. Anopheles quadrimaculatus and Cx. erraticus fed primarily upon mammalian hosts. Three avian species (the American Robin, the Common Grackle, and the Northern Cardinal) made up the majority of avian-derived bloodmeals, with the American Robin representing the most frequently fed upon avian host. An analysis of these host feeding data using a modification of a transmission model for Eastern Equine encephalitis virus suggested that the American Robin and Common Grackle represented the most important reservoir hosts for West Nile virus. A temporal analysis of the feeding patterns of the dominant Culex species did not support a shift in feeding behavior away from robins to mammals late in the summer. However, a significant degree of temporal variation was noted in the proportion of robin-derived bloodmeals when the data were analyzed by semi-monthly periods throughout the summers of 2002 and 2003. This pattern was consistent with the hypothesis that the mosquitoes were preferentially feeding upon nesting birds.

  9. Mania associated with interferon α2b treatment

    Directory of Open Access Journals (Sweden)

    Basanth K

    2006-01-01

    Full Text Available Neuropsychiatric side effects are common with Interferon α 2b. Psychosis and depression have been reported. Several cases of mania have been reported but only few have been associated with treatment for hepatitis B. We report a case of mania with psychotic symptoms in a 21-year-old female diagnosed to have hepatitis-B infection, who was receiving interferon. The report supports the view that dose reductions or pauses during interferon treatment can cause mania. Family history of mood disorder could be a risk factor. Atypical presentations are common in interferon-induced mania. Mania induced by interferon responds well to antimanic drugs. Since the use of interferon is increasing in developing countries, the need for awareness of side effects and management issues are important and these are highlighted.

  10. Semantic ETL into i2b2 with Eureka!

    Science.gov (United States)

    Post, Andrew R; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H

    2013-01-01

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns' complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud.

  11. Relationship Quality as Predictor of B2B Customer Loyalty

    Directory of Open Access Journals (Sweden)

    Shaimaa S. B. Ahmed Doma

    2013-02-01

    Full Text Available Relationship marketing has become extremely important recently due to the fierce competition in today's marketplace. Companies are required to build long-term profitable relationship with customers and to achieve customer loyalty. Also, switching behaviors frequently occur among most of targeted customers. Fewer studies, however, discuss the effects of relationship quality efforts on customer loyalty. Therefore, this study is aimed to investigate the impact of relationship quality on customer loyalty in B2B context in the Egyptian shipping services sector. Building on prior research, we propose relationship quality as a higher construct comprising trust, commitment and satisfaction. An analytical model is developed as a guideline to test the relationships between relationship quality dimensions and customer loyalty.

  12. Strategic Insights from Mystery Shopping in B2B Relationships

    DEFF Research Database (Denmark)

    Mattsson, Jan

    2012-01-01

    This paper describes how mystery shopping can be used to gain valuable strategic input in B2B service relationships. We account for a longitudinal case study framed as a natural experiment (duration 18 months) in a Swedish group of consultancy companies offering a wide selection of industrial...... services to large Scandinavian corporations. We account for and analyse the process of building a mystery shopping procedure to get strategic insights from engineers delivering temporary consultancy services to these clients. After a successful trial period with three mystery shoppers the experiment (a...... guideline covering the themes of map, smoke and mirror as metaphors) has been extended to comprise a larger group of engineers and may be taken up in a company-wide way. The experiment was deemed effective in developing both a procedure for mystery shopping and a new way to train the consultants....

  13. Vortex lattice transitions in YNi2B2C

    Indian Academy of Sciences (India)

    S J Levett; C D Dewhurst; D McK Paul

    2002-05-01

    We have performed extensive small-angle neutron scattering (SANS) diffraction studies of the vortex lattice in single crystal YNi2B2C for $B||c$. High-resolution SANS, combined with a field-oscillation vortex lattice preparation technique, allows us to separate Bragg scattered intensities from two orthogonal domains and accurately determine the unit cell angle, . The data suggest that upon increasing field there is a finite transition width where both low- and high-field distorted hexagonal vortex lattice phases, mutually rotated by 45°, coexist. The smooth variation of diffracted intensity from each phase through the transition corresponds to a redistribution of populations between the two types of domains.

  14. Getting started with Oracle SOA B2B Integration a hands-on tutorial

    CERN Document Server

    Bhatia, Krishnaprem; Perlovsky, Alan

    2013-01-01

    This hands on tutorial gives you the best possible start you could hope for with Oracle B2B. Learn using real life scenarios and examples to give you a solid footing of B2B.This book is for B2B architects, consultants and developers who would like to design and develop B2B integrations using Oracle B2B. This book assumes no prior knowledge of Oracle B2B and explains all concepts from scratch using illustrations, real world examples and step-by-step instructions. The book covers enough depth and details to be useful for both beginner and advanced B2B users.

  15. Structure of human nucleosome containing the testis-specific histone variant TSH2B

    Energy Technology Data Exchange (ETDEWEB)

    Urahama, Takashi; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi, E-mail: kurumizaka@waseda.jp [Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan)

    2014-03-25

    The crystal structure of human nucleosome containing the testis-specific TSH2B variant has been determined. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, and induces a local structural difference between TSH2B and H2B in nucleosomes. The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

  16. Effects of (Cr,Fe){sub 2}B borides on hardness in powder-injection-molded product fabricated with Fe-based alloy powders

    Energy Technology Data Exchange (ETDEWEB)

    Do, Jeonghyeon; Jeon, Changwoo; Paul Kim, Choongnyun; Lee, Byeong-Joo [Center for Advanced Aerospace Material, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Lee, Sunghak, E-mail: shlee@postech.ac.kr [Center for Advanced Aerospace Material, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Lee, Eon-Sik [Advanced Metallic Materials Research Department, Research Institute of Industrial Science and Technology, Pohang 790-330 (Korea, Republic of); Shik Yoon, Tae [Bestner Co., 146-8 Sangdaewon-dong, Sungnam 462-121 (Korea, Republic of); Su Shin, Yang [New Growth Technology Strategy Department, POSCO, Seoul 135-777 (Korea, Republic of)

    2012-10-30

    In the present study, a powder injection molding (PIM) product containing (Cr,Fe){sub 2}B borides was fabricated with Fe-based alloy powders, and its microstructure and hardness were investigated in relation with volume fraction of (Cr,Fe){sub 2}B. In the Fe-based alloys designed by the thermodynamic calculation, the volume fractions of (Cr,Fe){sub 2}B increased with increasing (X{sub Cr}+X{sub B}) value, and were well matched with those obtained from the thermodynamic calculation. The hardness of the Fe-based alloys linearly increased with increasing volume fraction of (Cr,Fe){sub 2}B. When Fe-based alloy powders were injection-molded and sintered at 1165 Degree-Sign C, a densified microstructure with almost no pores was obtained. In the sintered microstructure, 56 vol% of (Cr,Fe){sub 2}B borides, together with a few pores (porosity; 0.5%), were relatively homogeneously distributed in the tempered martensite matrix, which resulted in the very high hardness over 600 VHN. Such a high hardness suggested that the present Fe-based alloy powders could be readily adopted for fabricating PIM products or for replacing conventional stainless steel PIM products.

  17. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2012-04-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.         JEL Codes: D23, L86Keywords: Cost, Transaction Costs, Transactions

  18. Long-term efficacy and safety of interferon-alpha-2B in patients with mumps orchitis.

    Science.gov (United States)

    Yapanoglu, Turgut; Kocaturk, Huseyin; Aksoy, Yilmaz; Alper, Fatih; Ozbey, Isa

    2010-12-01

    The aim of this study was to determine long-term efficacy and safety subcutaneous injection of interferon-alpha-2B in patients with mumps orchitis in terms of testicular volume and other testicular functions. Mumps orchitis was evaluated in 37 patients. Patients were hospitalized and administered 1 × 3,000,000 IU subcutaneous injection of interferon-alpha-2B daily for 7 days. The testicular volumes of all the patients were measured by ultrasonography in the 18th month following treatment termination. The testes volumes were evaluated by descriptive statistics as percentages. Patients were divided into three groups according to testes volumes and differences between the involved and non-involved testicles. Group I included patients with normal testes volume (> 12 ml) and a difference between testes of less than 2 ml or 20%; Group II (atrophic groups) included patients with testes volume of less than 12 ml; and Group III (hypotrophic groups) included patients with testes volume of greater than 12 ml and a difference between testes of more than 2 ml or 20%. Groups were compared in terms of results of semen analysis and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Patients' ages ranged between 17 and 41 years (mean: 28.3 years). A total of nine atrophy cases were identified. Sixteen patients were determined to have hypotrophic testes with a difference of 2-10 ml or 20% between the involved and non-involved testicles, despite the absence of testicular atrophy. A comparison of groups revealed that sperm density, total sperm count, total motile sperm count, and motility percentage were significantly higher in Group I than in the other groups, while serum FSH and LH levels were lower in Group I than in the other groups. Although the use of interferon-alpha-2B appears to prevent testicular atrophy and protect testicular function, it leads to a considerable difference in the volume between testicles and a significant loss of testicular

  19. Efficient cell culture system for hepatitis C virus genotype 2B

    DEFF Research Database (Denmark)

    2014-01-01

    The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from...... transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analysis.......The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2...

  20. Phonon linewidths in YNi2B2C

    Indian Academy of Sciences (India)

    L Pintschovius; F Weber; W Reichardt; A Kreyssig; R Heid; D Reznik; O Stockert; K Hradil

    2008-10-01

    Phonons in a metal interact with conduction electrons which give rise to a finite linewidth. In the normal state, this leads to a Lorentzian shape of the phonon line. Density functional theory is able to predict the phonon linewidths as a function of wave vector for each branch of the phonon dispersion. An experimental verification of such predictions is feasible only for compounds with very strong electron–phonon coupling. YN2B2C was chosen as a test example because it is a conventional superconductor with a fairly high c (15.2 K). Inelastic neutron scattering experiments did largely confirm the theoretical predictions. Moreover, they revealed a strong temperature dependence of the linewidths of some phonons with particularly strong electron–phonon coupling which can as yet only qualitatively be accounted for by theory. For such phonons, marked changes of the phonon frequencies and linewidths were observed from room temperature down to 15 K. Further changes were observed on entering into the superconducting state. These changes can, however, not be described simply by a change of the phonon linewidth.

  1. Natural releases from contaminated groundwater, Example Reference Biosphere 2B

    Energy Technology Data Exchange (ETDEWEB)

    Simon, I. [CIEMAT/PIRA, Avda Complutense 22, 28040 Madrid (Spain)]. E-mail: isc@csn.es; Naito, M. [Nuclear Waste Management Organization of Japan (NUMO), 4-1-23 Shiba, Minato-ku, Tokyo, 108-0014 (Japan); Thorne, M.C. [Mike Thorne and Associates Limited, Abbotsleigh, Kebroyd Mount, Ripponden, Halifax, West Yorkshire HX6 3JA (United Kingdom); Walke, R. [Enviros QuantiSci, Building D5, Culham Science Centre, Culham, Oxfordshire OX14 3DB (United Kingdom)

    2005-07-01

    Safety assessment is a tool which, by means of an iterative procedure, allows the evaluation of the performance of a disposal system and its potential impact on human health and the environment. Radionuclides from a deep geological disposal facility may not reach the surface environment until many tens of thousands of years after closure of the facility. The BIOMASS Programme on BIOsphere Modelling and ASSessment developed Examples of 'Reference Biospheres' to illustrate the use of the methodology and to demonstrate how biosphere models can be developed and justified as being fit for purpose. The practical examples are also intended to be useful in their own right. The Example Reference Biosphere 2B presented here involves the consideration of alternative types of geosphere-biosphere interfaces and calculation of doses to members of hypothetical exposure groups arising from a wide range of exposure pathways within agricultural and semi-natural environments, but without allowing for evolution of the corresponding biosphere system. The example presented can be used as a generic analysis in some situations although it was developed around a relatively specific conceptual model. It should be a useful practical example, but the above numerical results are not intended to be understood as prescribed biosphere 'conversion factors'.

  2. Analysis of exoplanet XO-2 b observed with HST NICMOS

    Science.gov (United States)

    Crouzet, Nicolas; McCullough, P. R.; Burke, C.; Long, D.

    2011-09-01

    We present the photometric and spectroscopic analysis of the transiting planet XO-2 b, from HST NICMOS. Three transits of the planet have been observed. The field of view contains not only the XO-2 star but also a second star of very similar properties, which we use as a comparison star. We first perform a white-light photometric analysis of the data. The high signal to noise ratio yields improved parameters for the planet and host star. We then build the spectrum of this system in the range 1.2-1.8 microns with a spectral resolution of R 35, taking into account systematic effects. To investigate the validity of the method and the reliability of NICMOS data, we also build a spectrum for the exoplanet XO-1 b. We find an overall shape close to Tinetti et al. (ApJL 2010), although differences appear for some particular features. In the context of a debate about planetary spectra obtained with NICMOS, this study suggests that NICMOS data, although clearly affected by systematics, contain enough information to derive planetary spectra at least at low resolution.

  3. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Liangyou; Rui

    2014-01-01

    The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.

  4. Lack of genetic association between OCT1, ABCB1, and UGT2B7 variants and morphine pharmacokinetics

    DEFF Research Database (Denmark)

    Nielsen, L M; Sverrisdóttir, E; Bjerregaard Stage, T

    2017-01-01

    (CL), and volume of distribution (VD). The area under the plasma concentration-time curve (AUC0-150min) and the maximum plasma concentration (Cmax) were also calculated. Pharmacodynamic data were measured as pain tolerance thresholds to mechanical stimulation of the rectum and muscle, as well as tonic...... cold pain stimulation ("the cold pressor test" where hand was immersed in cold water). Six different single nucleotide polymorphisms in three different genes (OCT1 (n=22), ABCB1 (n=37), and UGT2B (n=22)) were examined. RESULTS: Neither AUC0-150min, ktr, CL, nor VD were associated with genetic variants...... in OCT1, ABCB1, and UGT2B7 (all P>0.05). Similarly, the antinociceptive effects of morphine on rectal, muscle, and cold pressor tests were not associated with these genetic variants (all P>0.05). CONCLUSIONS: In this experimental study in healthy volunteers, we found no association between different...

  5. Lithium decreased NR2B tyrosine phosphorylation and interactions of NR2B and PSD-95 with Src in rat hippocampus following cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To study the effects of chronic lithium on N-methyl-d-aspartate receptor subunit 2B (NR2B) tyrosine phosphorylation and the interactions of NR2B and PSD-95 with Src induced by cerebral ischemia/reperfusion (I/R). Methods: Transient (15 min) cerebral ischemia was induced by four-vessel occlusion procedure in SD rats. Immunoprecipitation (IP) and immunoblotting (IB)were performed to investigate the phosphorylation and interactions of proteins. The effects of lithium on tyrosine phosphorylation of NR2B and its interactions with PSD-95 and Src were examined. Results: Transient cerebral ischemia 15 min followed by reperfusion 6 h (I/R 6h) caused a significant increase in tyrosine phosphorylation of NR2B. Administration of LiCl for 7days before ischemia caused a profound decrease in tyrosine phosphorylation of NR2B. Similiarly, the interactions of NR2B and PSD-95 with Src were also enhanced by I/R 6 h.moreover, these interactions were also inhibited by chronic lithium. Conclusion: Pretreatment with lithium decrease tyrosine phosphorylation of NR2B and interactions of NR2B and PSD-95 with Src during cerebral I/R.

  6. GluN2B-containing NMDA receptors promote glutamate synapse development in hippocampal interneurons.

    Science.gov (United States)

    Kelsch, Wolfgang; Li, Zhijun; Wieland, Sebastian; Senkov, Oleg; Herb, Anne; Göngrich, Christina; Monyer, Hannah

    2014-11-26

    In postnatal development, GluN2B-containing NMDARs are critical for the functional maturation of glutamatergic synapses. GluN2B-containing NMDARs prevail until the second postnatal week when GluN2A subunits are progressively added, conferring mature properties to NMDARs. In cortical principal neurons, deletion of GluN2B results in an increase in functional AMPAR synapses, suggesting that GluN2B-containing NMDARs set a brake on glutamate synapse maturation. The function of GluN2B in the maturation of glutamatergic inputs to cortical interneurons is not known. To examine the function of GluN2B in interneurons, we generated mutant mice with conditional deletion of GluN2B in interneurons (GluN2B(ΔGAD67)). In GluN2B(ΔGAD67) mice interneurons distributed normally in cortical brain regions. After the second postnatal week, GluN2B(ΔGAD67) mice developed hippocampal seizures and died shortly thereafter. Before the onset of seizures, GluN2B-deficient hippocampal interneurons received fewer glutamatergic synaptic inputs than littermate controls, indicating that GluN2B-containing NMDARs positively regulate the maturation of glutamatergic input synapses in interneurons. These findings suggest that GluN2B-containing NMDARs keep the circuit activity under control by promoting the maturation of excitatory synapses in interneurons.

  7. Beyond the exchange--the future of B2B.

    Science.gov (United States)

    Wise, R; Morrison, D

    2000-01-01

    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important.

  8. Hanstholm phase 2B. Offshore wave energy test 1994 - 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-01

    The wave power converter consists of a float 2.5 meter in diameter, connected by a rope to a seabed-mounted piston pump, installed on 25 meter deep water 2,5 km offshore Hanstholm, Denmark. The converter is designed to absorb an average maximum power of 1 kW. Measured data in real sea conditions are compared to results based on computer simulations and previous tank testing. Losses caused by rope elasticity and hysteresis, friction in the pump and back flow through the valves are assessed. The economic perspectives of a large wave power plant are presented, based on a revised prototype incorporating the results and experience gained during the test period. The wave energy conversion test `Hanstholm phase 2B` has showed, that it it technically possible to exploit the offshore wave energy resource. This source of energy could become attractive for commercial enterprise. The wave power converter demonstrated a reliable performance over a period of nine months. It produced energy under all wave conditions and survived storm waves of 9,6 m. A 300 MW wave power plant in the Danish part of the North sea is estimated to produce electricity at a cost between 2,1 - 2,4 DKK/kWh. The electrical transmission to shore contribute to approximately 20% of the cost. New data predict a potential of 23 kW per meter wave front. The energy plan Energy 21 proposed by the Danish Department of Energy, includes a scenario incorporating wave energy in the energy system year 2030. A strategy for the development of wave energy, has been proposed as part of the project OWEC-1 supported by the European Joule R and D programme. A proposal for future Danish initiatives to develop second generation point absorber systems is outlined. (ARW) 29 refs.

  9. Metastable Equilibria for the Quaternary System Li2B4O7+ Na2B4O7+K2B4O7+H2Oat15℃

    Institute of Scientific and Technical Information of China (English)

    SANG,Shi-Hua; YIN,Hui-An; NI,Shi-Jun; DENG,Miao

    2008-01-01

    Metastable equilibrium solubilities and such physico-chemical properties as densities, conductivity, pH, refractive index and viscosity of the solution for the quaternary system Li2B4O7+Na2B4O7+K2B4O7+H2O at 15℃ were determined experimentally. According to the experimental data, the metastable equilibrium phase diagram was plotted. In the metastable phase diagram, there are one invariant point, three univariant curves, and three fields of crystallization: Li2B2O4·16H2O, Na2B4O7·10H2O, and K2B4O7·4H2O. Potassium borate (K2B4O7·4H2O) has the smallest crystallization field and sodium borate (borax) has the biggest one. Also, the relationship diagram between the properties and the ion concentration of solution was constructed. It can be seen from the relationship diagram that the metastable equilibrium solution density values, viscosity values and refractive index values are increased apparently with the rise of lithium borate concentration, reaching the maximum values at invariant point F. Electrical conductivity values and pH values, however, fall down with the rise of ion concentration on the whole.

  10. Data of evolutionary structure change: 1CLMA-2B1UA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CLMA-2B1UA 1CLM 2B1U A A LTEEQIAEFKEAFALFD-KDGDGTITTKELGTVMRSLGQ...NPTEAELQDMINEVDADGNGTIDFPEFLSLMARKMKEQDSEEELIEAFKVFDRDGNGLISAAELRHVMTNLGEKLTDDEVDEMIREADIDGDGHINYEEFVRMMVS 1CLM A 1CLMA FALFD-KDGDG

  11. Data of evolutionary structure change: 1BHNF-2B8PB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BHNF-2B8PB 1BHN 2B8P F B ANSERTFIAIKPDGVQRGLIGEIIKRFEQKGFRLVAMKF...NWIYE -GLQRTLVLIKPDAFERSLVAEIMGRIEKKNFKIVSMKFWSKAPRNLIEQHYKEHSEQSYFNDNCDFMVSGPIISIVYEGTDAISKIRR...------------ EVID>EVID> 0 1BHN F 1BHNF FMRAS-ED

  12. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

    DEFF Research Database (Denmark)

    Clayton, Emma L.; Mizielinska, Sarah; Edgar, James R.;

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The a...

  13. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

    DEFF Research Database (Denmark)

    Clayton, Emma L.; Mizielinska, Sarah; Edgar, James R.

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The a...

  14. File list: Pol.ALL.50.Polr2b.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.ALL.50.Polr2b.AllCell mm9 RNA polymerase Polr2b All cell types SRX373045,SRX595...04153,SRX119655,SRX318115,SRX373044,SRX119652,SRX318112 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.ALL.50.Polr2b.AllCell.bed ...

  15. TGF- induces Lysyl hydroxylase 2b in human synovial osteoarthritic fibroblasts through ALK5 signaling

    NARCIS (Netherlands)

    Remst, Dennis F. G.; Davidson, Esmeralda N. Blaney; Vitters, Elly L.; Bank, Ruud A.; van den Berg, Wim B.; van der Kraan, Peter M.

    2014-01-01

    Lysyl hydroxylase 2b (LH2b) is known to increase pyridinoline cross-links, making collagen less susceptible to enzymatic degradation. Previously, we observed a relationship between LH2b and osteoarthritis-related fibrosis in murine knee joint. For this study, we investigate if transforming growth fa

  16. File list: His.PSC.50.H2B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.50.H2B.AllCell mm9 Histone H2B Pluripotent stem cell SRX1034714,SRX1034721,...SRX1034715,SRX1034720 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.PSC.50.H2B.AllCell.bed ...

  17. Incidence and prevalence of multiple endocrine neoplasia 2B in Denmark

    DEFF Research Database (Denmark)

    Mathiesen, Jes Sloth; Kroustrup, Jens Peter; Vestergaard, Peter

    2017-01-01

    Extract: Multiple endocrine neoplasia 2B (MEN2B) is an autosomal dominant inherited cancer syndrome associating medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), ganglioneuromatosis of the aerodigestive tract and facial, ophthalmologic and skeletal abnormalities. MEN2B is caused by the M...

  18. Data of evolutionary structure change: 1BHNF-2B8PA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BHNF-2B8PA 1BHN 2B8P F A ANSERTFIAIKPDGVQRGLIGEIIKRFEQKGFRLVAMKF...NWIYE -GLQRTLVLIKPDAFERSLVAEIMGRIEKKNFKIVSMKFWSKAPRNLIEQHYKE-----YFNDNCDFMVSGPIISIVYEGTDAISKIRR...------------- EVID>EVID> 0 ... 1BHN F 1BHNF FMRAS-E...5856934 EVID> 1 2B8P

  19. ab initio calculation study on vibrational spectra of C2B10H12,NB11H12 and C2B10H11Cl

    Institute of Scientific and Technical Information of China (English)

    于微舟; 张明瑜; 孙家钟

    1996-01-01

    Geometrical optimization and theoretical calculation of the vibrational frequencies have been performed for C2B10H12, NB11H12 and C2B10Cl by using Gaussian 92 program at 6-31G basis set. The results obtained in this work are in agreement with experimental ones. The optimized geometry and vibrational spectra show that the icosahedral configuration remains unchanged upon converting from B12H122- to the title compounds. The vibrational spectrum of C2B10H11Cl features the absence of C-Cl stretching vibration. But the (C2B10H11)-Cl vibration mode in the low frequency region is as the case for two-atom molecules if the group (C2B10H11) is considered as a pseudoatom

  20. Vortex phase diagram studies in the weakly pinned single crystals of YNi2B2C and LuNi2B2C

    Indian Academy of Sciences (India)

    D Jaiswal-Nagar; D Pal; M R Eskildsen; P C Canfield; H Takeya; S Ramakrishnan; A K Grover

    2006-01-01

    We present a study of magnetization measurements performed on the single crystals of YNi2B2C and LuNi2B2C. For both the compounds, we find flux jumps in magnetisation values in the respective field regions, where the structural transitions in the flux line lattice symmetry have been reported in these systems via the small angle neutron scattering experiments. The magnetisation hysteresis loops and the AC susceptibility measurements show pronounced peak effect as well as second magnetisation peak anomaly for both YNi2B2C and LuNi2B2C. Based on these results, a vortex phase diagram has been constructed for YNi2B2C for $H \\Arrowvert c$ depicting different glassy phases of the vortex matter.

  1. Functional role of human NK cell receptor 2B4 (CD244) isoforms.

    Science.gov (United States)

    Mathew, Stephen O; Rao, Krithi K; Kim, Jong R; Bambard, Nowland D; Mathew, Porunelloor A

    2009-06-01

    2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses.

  2. Role of adenosine A2b receptor overexpression in tumor progression.

    Science.gov (United States)

    Sepúlveda, Cesar; Palomo, Iván; Fuentes, Eduardo

    2016-12-01

    The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells. Therefore, adenosine A2b receptor appears as an interesting therapeutic target for cancer treatment.

  3. PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia.

    Science.gov (United States)

    Zhang, Meijuan; Li, Qingjie; Chen, Ling; Li, Jie; Zhang, Xin; Chen, Xiang; Zhang, Qingxiu; Shao, Yuan; Xu, Yun

    2014-08-01

    Modification of N-methyl-d-aspartate receptor (NMDAR)-mediated excitotoxicity appears to be a potential target in the treatment of ischemic stroke. Postsynaptic density protein-93 (PSD-93) specifically binds the C-terminal tails of the NMDAR, which is critical to couple NMDAR activity to specific intracellular signaling. This study is to investigate whether PSD-93 disruption displays neuroprotection in a focal ischemic stroke model of adult mice and, if it does, to explore possible mechanisms. It was found that, following middle cerebral artery occlusion (MCAO), PSD-93 knockout (KO) mice manifested significant reductions in infarcted volume, neurological deficits and number of degenerated neurons. PSD-93 deletion also reduced cultured cortical neuronal death caused by glucose and oxygen deprivation (OGD). Ischemic long term potentiation (i-LTP) could not be induced in the PSD-93 KO group and wild type (WT) groups pretreated with either AP-5 (NMDAR inhibitor) or PP2 (Src family inhibitor). PSD-93 KO decreased the phosphorylation of the NR2B at Tyr1472 and the interaction between NR2B and Fyn after MCAO. Together, our study demonstrated that PSD-93 KO confers profound neuroprotection against ischemic brain injury, which probably links to the inhibitory effect on Fyn-mediated phosphorylation of NR2B caused by PSD-93 deletion. These findings may provide a novel avenue for the treatment of ischemic stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Copy Number Variation of UGT 2B Genes in Indian Families Using Whole Genome Scans

    Directory of Open Access Journals (Sweden)

    Avinash M. Veerappa

    2016-01-01

    Full Text Available Background and Objectives. Uridine diphospho-glucuronosyltransferase 2B (UGT2B is a family of genes involved in metabolizing steroid hormones and several other xenobiotics. These UGT2B genes are highly polymorphic in nature and have distinct polymorphisms associated with specific regions around the globe. Copy number variations (CNVs status of UGT2B17 in Indian population is not known and their disease associations have been inconclusive. It was therefore of interest to investigate the CNV profile of UGT2B genes. Methods. We investigated the presence of CNVs in UGT2B genes in 31 members from eight Indian families using Affymetrix Genome-Wide Human SNP Array 6.0 chip. Results. Our data revealed >50% of the study members carried CNVs in UGT2B genes, of which 76% showed deletion polymorphism. CNVs were observed more in UGT2B17 (76.4% than in UGT2B15 (17.6%. Molecular network and pathway analysis found enrichment related to steroid metabolic process, carboxylesterase activity, and sequence specific DNA binding. Interpretation and Conclusion. We report the presence of UGT2B gene deletion and duplication polymorphisms in Indian families. Network analysis indicates the substitutive role of other possible genes in the UGT activity. The CNVs of UGT2B genes are very common in individuals indicating that the effect is neutral in causing any suspected diseases.

  5. Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn Phox2b heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Nelina eRamanantsoa

    2011-09-01

    Full Text Available The Phox2b gene is necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/- pups and their wild-type littermates (Phox2b+/+ to hypoxia (10% O2 or hypercapnia (8% CO2 under thermoneutral (33°C or cold (26°C conditions. We found that Phox2b+/- pups showed less normoxic ventilation (VE in the cold than Phox2b+/+ pups. Phox2b+/- pups also showed lower oxygen consumption (VO2 in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/- pups. Finally, because serotonin (5-HT neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high-pressure liquid chromatography, and found that it was altered in Phox2b+/- pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.

  6. The brain-specific neural zinc finger transcription factor 2b (NZF-2b/7ZFMyt1 suppresses cocaine self-administration in rats

    Directory of Open Access Journals (Sweden)

    Vijay Chandrasekar

    2010-04-01

    Full Text Available Brain-specific neural-zinc-finger transcription factor-2b (NZF2b/7ZFMyt1 is induced in the mesolimbic dopaminergic region after chronic cocaine exposure and lentiviral-mediated expression of NZF2b/7ZFMyt1 in the nucleus accumbens results in decreased locomotor activity (Chandrasekar and Dreyer, 2009. In this study the role of NZF2b/7ZFMyt1 in active cocaine seeking and of its interaction with histone deacetylase on the altered behavior has been observed. Localized expression of NZF2b/7ZFMyt1 in the nucleus accumbens resulted in attenuated cocaine self-administration, whereas silencing this transcription factor with lentiviruses expressing siRNAs increased the animal′s motivation to self-infuse cocaine. Low doses of sodium butyrate, a potent inhibitor of histone deacetylase, were sufficient to reverse the NZF2b/7ZFMyt1-mediated decrease in cocaine self-administration. NZF2b/7ZFMyt1 expression resulted in strong induction of transcription factors REST1 and NAC1 and of the dopamine D2 receptor, with concomitant inhibition of BDNF and its receptor TrkB. We show that NZF2b/7ZFMyt1 colocalizes with histone deacetylase-2 (HDAC2, probably overcoming the suppression of transcriptional activity caused by Lingo1. These findings show that molecular adaptations mediated by NZF2b/7ZFMyt1 expression possibly lead to decreased responsiveness to the reinforcing properties of cocaine and play a prominent role in affecting the behavioral changes induced by the drug.

  7. Nrk2b-mediated NAD+ production regulates cell adhesion and is required for muscle morphogenesis in vivo: Nrk2b and NAD+ in muscle morphogenesis.

    Science.gov (United States)

    Goody, Michelle F; Kelly, Meghan W; Lessard, Kevin N; Khalil, Andre; Henry, Clarissa A

    2010-08-15

    Cell-matrix adhesion complexes (CMACs) play fundamental roles during morphogenesis. Given the ubiquitous nature of CMACs and their roles in many cellular processes, one question is how specificity of CMAC function is modulated. The clearly defined cell behaviors that generate segmentally reiterated axial skeletal muscle during zebrafish development comprise an ideal system with which to investigate CMAC function during morphogenesis. We found that Nicotinamide riboside kinase 2b (Nrk2b) cell autonomously modulates the molecular composition of CMACs in vivo. Nrk2b is required for normal Laminin polymerization at the myotendinous junction (MTJ). In Nrk2b-deficient embryos, at MTJ loci where Laminin is not properly polymerized, muscle fibers elongate into adjacent myotomes and are abnormally long. In yeast and human cells, Nrk2 phosphorylates Nicotinamide Riboside and generates NAD+ through an alternative salvage pathway. Exogenous NAD+ treatment rescues MTJ development in Nrk2b-deficient embryos, but not in laminin mutant embryos. Both Nrk2b and Laminin are required for localization of Paxillin, but not beta-Dystroglycan, to CMACs at the MTJ. Overexpression of Paxillin in Nrk2b-deficient embryos is sufficient to rescue MTJ integrity. Taken together, these data show that Nrk2b plays a specific role in modulating subcellular localization of discrete CMAC components that in turn plays roles in musculoskeletal development. Furthermore, these data suggest that Nrk2b-mediated synthesis of NAD+ is functionally upstream of Laminin adhesion and Paxillin subcellular localization during MTJ development. These results indicate a previously unrecognized complexity to CMAC assembly in vivo and also elucidate a novel role for NAD+ during morphogenesis. Copyright 2010 Elsevier Inc. All rights reserved.

  8. NR2B antagonist CP-101,606 inhibits NR2B phosphorylation at tyrosine-1472 and its interactions with Fyn in levodopa-induced dyskinesia rat model.

    Science.gov (United States)

    Kong, Min; Ba, Maowen; Liu, Chuanyu; Zhang, Yanxiang; Zhang, Hongli; Qiu, Haiyan

    2015-04-01

    The augmented tyrosine phosphorylation of NR2B subunit of N-methyl-d-aspartate receptors (NMDAR) dependent on Fyn kinase has been associated with levodopa (l-dopa)-induced dyskinesia (LID). CP-101,606, one selective NR2B subunit antagonist, can improve dyskinesia. Yet, the accurate action mechanism is less well understood. In the present study, the evidences were investigated. Valid 6-hydroxydopamine-lesioned parkinsonian rats were treated with l-dopa intraperitoneally for 22 days to induce LID rat model. On day 23, rats received either CP-101,606 (0.5mg/kg) or vehicle with each l-dopa dose. On the day of 1, 8, 15, 22, and 23 during l-dopa treatment, we determined abnormal involuntary movements (AIMs) in rats. The levels of NR2B phosphorylation at tyrosine-1472 (pNR2B-Tyr1472) and interactions of NR2B with Fyn in LID rat model were detected by immunoblotting and immunoprecipitation. Results showed that CP-101,606 attenuated l-dopa-induced AIMs. In agreement with behavioral analysis, CP-101,606 reduced the augmented pNR2B-Tyr1472 and its interactions with Fyn triggered during the l-dopa administration in the lesioned striatum of parkinsonian rats. Moreover, CP-101,606 also decreased the level of Ca(2+)/calmodulin-dependent protein kinase II at threonine-286 hyperphosphorylation (pCaMKII-Thr286), which was the downstream signaling amplification molecule of NMDAR overactivation and closely associated with LID. However, the protein level of NR2B and Fyn had no difference under the above conditions. These data indicate that the inhibition of the interactions of NR2B with Fyn and NR2B tyrosine phosphorylation may contribute to the CP-101,606-induced downregulation of NMDAR function and provide benefit for the therapy of LID. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

    Energy Technology Data Exchange (ETDEWEB)

    Wilderman, P. Ross, E-mail: pwilderman@ucsd.edu [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Jang, Hyun-Hee [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Malenke, Jael R. [Department of Biology, University of Utah, Salt Lake City, UT (United States); Salib, Mariam; Angermeier, Elisabeth; Lamime, Sonia [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Dearing, M. Denise [Department of Biology, University of Utah, Salt Lake City, UT (United States); Halpert, James R. [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States)

    2014-02-01

    Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in Escherichia coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system. - Highlights: • Three CYP2B enzymes from Neotoma lepida were cloned, engineered, and expressed. • A mix of catalytic and binding assays yields unique results for each enzyme. • Mutational analysis indicates CYP{sub 2}B substrate recognition remains to be clarified. • Reported N. lepida gene

  10. Overexpression of SULT2B1b Promotes Angiogenesis in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Wen Chen

    2016-03-01

    Full Text Available Background/Aims: Overexpression of cytosolic sulfotransferase 2B1b (SULT2B1b has been commonly found in colorectal and hepatocellular carcinoma, suggesting that SULT2B1b might act as a potential oncogenic protein. However, its clinical significance and biological role in gastric cancer progression remain largely unknown. Methods: Expressions of SULT2B1b in clinical gastric cancer (GC samples were examined using qRT-PCR and Western blot. Results: SULT2B1b was markedly overexpressed in human GC samples, and positively correlated with vessel density and associated with poor clinical features. We also demonstrated that overexpression of SULT2B1b resulted in increased tumor angiogenesis and tumor growth in mouse GC models. In addition, ablation of SULT2B1b in human GC cells lines BGC823 and MKN45 decreased the capability of the cells to recruit endothelial cells. Moreover, depletion of SULT2B1b in GC cells reduced VEGF-A expression by downregulating SP1 and AP2. Conclusion: Our results suggested that the SULT2B1b-mediated angiogenic pathway could serve as biomarkers for GC diagnosis and prognosis, and suppressing SULT2B1b-mediated angiogenic signaling might be a promising strategy for developing novel GC treatment.

  11. X-ray powder diffraction studies and thermal behaviour of NaK 2B 9O 15, Na(Na .17K .83) 2B 9O 15, and (Na .80K .20)K 2B 9O 15

    Science.gov (United States)

    Bubnova, R.; Albert, B.; Georgievskaya, M.; Krzhizhanovskaya, M.; Hofmann, K.; Filatov, S.

    2006-09-01

    The crystal structures of NaK 2B 9O 15 ( a=9.1158(1) Å, b=6.6246(1) Å, c=20.6812(3) Å, β=94.080(1)°, R=0.047, R=0.059, R=0.026), Na(Na .17K .83) 2B 9O 15 ( a=9.0559(1) Å, b=6.6170(1) Å, c=20.5833(3) Å, β=94.228(2)°, R=0.053, R=0.068, R=0.026), and (Na .80K .20)K 2B 9O 15 ( a=9.1534(1) Å, b=6.6296(1) Å, c=20.7422(3) Å, β=94.071(1)°, Z=4, R=0.041, R=0.052, R=0.023) were refined in the monoclinic space groups P2 1/ c(Z=4) using X-ray powder diffraction data and the Rietveld method. These nonaborates are isostructural to K 3B 9O 15. Their crystal structure consists of a three-dimensional open framework built up from three crystallographically independent triborate groups. The alkali metal cations are located on three different sites in the voids of the framework. High-temperature X-ray diffraction studies show that NaK 2B 9O 15 decomposes at about 700 °C in accordance with the peritectic reaction NaK 2B 9O 15↔K 5B 19O 31+liquid. The thermal expansion of NaK 2B 9O 15 and Na(Na .17K .83) 2B 9O 15 is highly anisotropic. A similarity of the thermal and compositional (Na-K substitution) deformations of NaK 2B 9O 15 is revealed: heating of NaK 2B 9O 15 by 1 °C leads to the same deformations of the crystal structure as increasing the amount of K atoms in (Na 1-xK x) 3B 9O 15 by 0.04 at% K.

  12. Evaluation of NR2B peptide as subunit vaccines against experimental neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    WANG Gong-ming; TIAN Yu-ke; CHEN Jian-ping; TIAN Xu-bi; GAO Feng; YANG Hui; AN Ke; MA Guo-ping

    2007-01-01

    Background NR2B containing N-methyl-D-aspartate (NMDA) receptor plays an important role in the facilitation and maintenance of neuropathic pain. The discrete distribution of NR2B subunit in the central nervous system (CNS) may support reduced side effects of agents that act selectively at this site. Therefore, we investigated the hypothesis that a humoral autoimmune response targeting the NR2B subunit of NMDA receptor relieves pain like behaviours produced by peripheral injury.Methods Rats were immunized subcutaneously with NR2B-Keyhole Limpet Hemocyanin (NR2B-KLH) three times at two-week intervals. NR2B specific IgG titres in sera and cerebrospinal fluid were determined by indirect ELISA. Seven days after the third immunization, 2 of the 3 terminal branches of the sciatic nerve (tibial and common peroneal nerves) were tightly ligated. Behavioural testing was carried out on every other day after surgery, until 7 days after surgery. The lumbar spinal cord (L4-6) was removed on day 7 after ligation. The expression of NR2B protein in the lumbar spinal cord was determined using Western blotting.Results After the second vaccination, NR2B specific IgG in sera was detected to be >0.5 μg/ml in six of nine rats. After the third vaccination, all the immunized rats had >2.2 μg/ml. Titres of NR2B specific IgG in sera peaked 42 days post initial immunization and persisted for over 70 days. No NR2B specific IgG was detected in sera from PBS or KLH group.The behavioural thresholds in NR2B group were significantly higher than those in PBS and KLH groups on day 7 after ligation. NR2B specific IgG in CSF in NR2B group could not be detected on day 1 before spinal dissection; but could be detected on day 7 after surgery. The expression of NR2B protein in group NR2B was significantly lower than in PBS and KLH groups on day 7 after surgery.Conclusion The NR2B peptide could be used as a vaccine against neuropathic pain, which could be associated with reduction of NR2B protein in

  13. Genetic loss of SH2B3 in acute lymphoblastic leukemia

    Science.gov (United States)

    Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A.; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K.

    2013-01-01

    The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis. PMID:23908464

  14. Primary structure of the histone 2B gene in the white root rot fungus, Rosellinia necatrix.

    Science.gov (United States)

    Aimi, Tadanori; Taguchi, Hiroyuki; Morinaga, Tsutomu

    2002-12-01

    The nucleotide sequence of the histone 2B (H2B) gene in the white root rot fungus, Rosellinia necatrix, was determined. The gene has two introns in the coding region at positions conserved in the Neurospora crassa and Aspergillus nidulans H2B genes, but the third intron present in the H2B gene from N. crassa and A. nidulans is absent in the R. necatrix H2B gene. The amino acid sequence of the coding region of the R. necatrix gene resembled that of N. crassa and A. nidulans. Therefore, the third intron in the H2B gene of N. crassa and A. nidulans may have been inserted into the present position after species diversification.

  15. Allele and genotype frequencies of CYP2B6 in a Turkish population.

    Science.gov (United States)

    Yuce-Artun, Nazan; Kose, Gulcin; Suzen, H Sinan

    2014-06-01

    Increasing interest in cytochrome P450 2B6 (CYP2B6) genetic polymorphism was stimulated by revelations of a specific CYP2B6 genotype significantly affecting the metabolism of various drugs in common clinical use in terms of increasing drug efficacy and avoiding adverse drug reactions. The present study aimed to determine the frequencies of CYP2B6*4 CYP2B6*5, CYP2B6*6, CYP2B6*7 and CYP2B6*9 alleles in healthy Turkish individuals (n = 172). Frequencies of three single nucleotide polymorphisms were 516G>T (28%), 785A>G (33%), and 1459C>T (12%). The frequencies of CYP2B6*1, *4, *5, *6, *7, and *9 alleles were 54.3 (95% CI 49.04-59.56), 6.4% (95% CI 3.81-8.99), 11% (95% CI 7.69-14.31), 25.3% (95% CI 20.71-29.89), 0.87% (95% CI -0.11-1.85) and 2.0% (95% CI 0.52-3.48), respectively. Allele *6 was more frequent (25.3%) than the other variant alleles in Turkish subjects. The frequencies of CYP2B6*4, *5, *6, *7, and *9 alleles were similar to European populations but significantly different from that reported for Asian populations. This is the first study to document the frequencies of the CYP2B6*4, *5, *6, *7, *9 alleles in the healthy Turkish individuals and our results could provide clinically useful information on drug metabolism by CYP2B6 in Turkish population.

  16. Do self-service technologies affect interfirm relationships? A B2B perspective

    OpenAIRE

    Raechel Johns

    2014-01-01

    While considerable literature examines business-to business (B2B) relationships, the impact of technology on these relationships has lacked attention. IT has impacted the way businesses operate in a B2B context as well as influencing services by altering the way services are delivered. To understand the way in which Internet technology has impacted these B2B services, it is essential to examine its impact not only on business processes but on business relationships too. One technology, enable...

  17. B2B marketingová komunikace společnosti John Deere

    OpenAIRE

    2013-01-01

    The aim of this master's thesis is to evaluate the implementation of the B2B marketing strategy of John Deere on a specific example. The theoretical part of the thesis focuses on defining the basics of modern marketing communications. Next it deals with defining the concept of B2B marketing and related strategies. The practical part focuses on the characterisation of the agricultural machinery industry and the slovak agricultural sector. Further it includes the introduction of other B2B marke...

  18. Volume Entropy

    CERN Document Server

    Astuti, Valerio; Rovelli, Carlo

    2016-01-01

    Building on a technical result by Brunnemann and Rideout on the spectrum of the Volume operator in Loop Quantum Gravity, we show that the dimension of the space of the quadrivalent states --with finite-volume individual nodes-- describing a region with total volume smaller than $V$, has \\emph{finite} dimension, bounded by $V \\log V$. This allows us to introduce the notion of "volume entropy": the von Neumann entropy associated to the measurement of volume.

  19. Insights into CYP2B6-mediated drug–drug interactions

    Directory of Open Access Journals (Sweden)

    William D. Hedrich

    2016-09-01

    Full Text Available Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR and pregnane X receptor (PXR in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.

  20. Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis;

    2012-01-01

    BACKGROUND: Frontotemporal dementia is the second most common form of young-onset dementia after Alzheimer's disease, and several genetic forms of frontotemporal dementia are known. A rare genetic variant is caused by a point mutation in the CHMP2B gene. CHMP2B is a component of the ESCRT...... role in the pathogenesis of the disease. METHODS: In the present study, we used lentiviral vectors to efficiently knockdown CHMP2B by delivering microRNA embedded small hairpin RNAs. RESULTS: We show that CHMP2B can be efficiently knocked down in patient fibroblasts using an RNA interference approach...

  1. Enhanced lithium storage in a VO{sub 2}(B)-multiwall carbon nanotube microsheet composite prepared via an in situ hydrothermal process

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, M.M., E-mail: mmr543@uow.edu.a [Institute for Superconducting and Electronic Materials and ARC Centre of Excellence for Electromaterials Science, University of Wollongong, NSW 2522 (Australia); Wang Jiazhao [Institute for Superconducting and Electronic Materials and ARC Centre of Excellence for Electromaterials Science, University of Wollongong, NSW 2522 (Australia); Idris, Nurul Hayati [Institute for Superconducting and Electronic Materials and ARC Centre of Excellence for Electromaterials Science, University of Wollongong, NSW 2522 (Australia); Department of Science Physics, University of Malaysia Terengganu, Kuala Terengganu 20522 (Malaysia); Chen Zhixin [School of Mechanical, Mechatronic and Materials Engineering, University of Wollongong, NSW 2522 (Australia); Liu Huakun [Institute for Superconducting and Electronic Materials and ARC Centre of Excellence for Electromaterials Science, University of Wollongong, NSW 2522 (Australia)

    2010-12-30

    A novel VO{sub 2}(B)-multiwall carbon nanotube (MWCNT) composite with a sheet-like morphology was synthesized by a simple in situ hydrothermal process. The morphology and structural properties of the samples were investigated by X-ray diffraction (XRD), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). FE-SEM observations demonstrated that the nanosheets are frequently grown together in the form of bundles composed of numerous nanosheets, each with a smooth surface and a typical length of 300-500 nm, width of 50-150 nm, and thickness of 10-50 nm. Electrochemical measurements were carried out using different discharge cut-off voltages. Electrochemical tests show that the VO{sub 2}(B)-MWCNT composite cathode features long-term cycling stability and high discharge capacity (177 mAh g{sup -1}) in the voltage range of 2.0-3.25 V at 1 C with a capacity retention of 92% after 100 cycles. The electrochemical impedance spectra (EIS) indicate that the VO{sub 2}(B)-MWCNT composite electrode has very low charge-transfer resistance compared with pure VO{sub 2}(B), indicating the enhanced ionic conductivity of the VO{sub 2}(B)-MWCNT composite. The enhanced cycling stability is attributed to the fact that the VO{sub 2}(B)-MWCNT composite can prevent the aggregation of active materials, accommodate the large volume variation, and maintain good electronic contact. We strongly believe that the VO{sub 2}(B)-MWCNT composite can be considered as a potential cathode material for lithium-ion batteries.

  2. Structural and biophysical characterization of human cytochromes P450 2B6 and 2A6 bound to volatile hydrocarbons: analysis and comparison.

    Science.gov (United States)

    Shah, Manish B; Wilderman, P Ross; Liu, Jingbao; Jang, Hyun-Hee; Zhang, Qinghai; Stout, C David; Halpert, James R

    2015-04-01

    X-ray crystal structures of complexes of cytochromes CYP2B6 and CYP2A6 with the monoterpene sabinene revealed two distinct binding modes in the active sites. In CYP2B6, sabinene positioned itself with the putative oxidation site located closer to the heme iron. In contrast, sabinene was found in an alternate conformation in the more compact CYP2A6, where the larger hydrophobic side chains resulted in a significantly reduced active-site cavity. Furthermore, results from isothermal titration calorimetry indicated a much more substantial contribution of favorable enthalpy to sabinene binding to CYP2B6 as opposed to CYP2A6, consistent with the previous observations with (+)-α-pinene. Structural analysis of CYP2B6 complexes with sabinene and the structurally similar (3)-carene and comparison with previously solved structures revealed how the movement of the F206 side chain influences the volume of the binding pocket. In addition, retrospective analysis of prior structures revealed that ligands containing -Cl and -NH functional groups adopted a distinct orientation in the CYP2B active site compared with other ligands. This binding mode may reflect the formation of Cl-π or NH-π bonds with aromatic rings in the active site, which serve as important contributors to protein-ligand binding affinity and specificity. Overall, the findings from multiple techniques illustrate how drugs metabolizing CYP2B6 and CYP2A6 handle a common hydrocarbon found in the environment. The study also provides insight into the role of specific functional groups of the ligand that may influence the binding to CYP2B6.

  3. Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells

    OpenAIRE

    Helena Libalova; Pavel Rossner; Kristyna Vrbova; Tana Brzicova; Jitka Sikorova; Michal Vojtisek-Lom; Vit Beranek; Jiri Klema; Miroslav Ciganek; Jiri Neca; Katerina Pencikova; Miroslav Machala; Jan Topinka

    2016-01-01

    This study used toxicogenomics to identify the complex biological response of human lung BEAS-2B cells treated with organic components of particulate matter in the exhaust of a diesel engine. First, we characterized particles from standard diesel (B0), biodiesel (methylesters of rapeseed oil) in its neat form (B100) and 30% by volume blend with diesel fuel (B30), and neat hydrotreated vegetable oil (NEXBTL100). The concentration of polycyclic aromatic hydrocarbons (PAHs) and their derivatives...

  4. Comparative analysis of toxic responses of organic extracts from diesel and selected alternative fuels engine emissions in human lung BEAS-2B cells

    OpenAIRE

    Líbalová, Helena; Rossner, Pavel, Jr.; Vrbová, Kristýna; Brzicová, Táňa; Sikorová, Jitka; Vojtíšek-Lom, Michal; Beranek, Vít; Kléma, Jiří; Ciganek,Miroslav; Neča, Jiří; Pěnčíková, Kateřina; Machala, Miroslav; Topinka, Jan

    2016-01-01

    This study used toxicogenomics to identify the complex biological response of human lung BEAS-2B cells treated with organic components of particulate matter in the exhaust of a diesel engine. First, we characterized particles from standard diesel (B0), biodiesel (methylesters of rapeseed oil) in its neat form (B100) and 30% by volume blend with diesel fuel (B30), and neat hydrotreated vegetable oil (NEXBTL100). The concentration of polycyclic aromatic hydrocarbons (PAHs) and their derivatives...

  5. Regulation of PI-2b Pilus Expression in Hypervirulent Streptococcus agalactiae ST-17 BM110

    Science.gov (United States)

    du Merle, Laurence; Rosinski-Chupin, Isabelle; Gominet, Myriam; Bellais, Samuel; Poyart, Claire; Trieu-Cuot, Patrick

    2017-01-01

    The widely spread Streptococcus agalactiae (also known as Group B Streptococcus, GBS) “hypervirulent” ST17 clone is strongly associated with neonatal meningitis. The PI-2b locus is mainly found in ST17 strains but is also present in a few non ST17 human isolates such as the ST-7 prototype strain A909. Here, we analysed the expression of the PI-2b pilus in the ST17 strain BM110 as compared to the non ST17 A909. Comparative genome analyses revealed the presence of a 43-base pair (bp) hairpin-like structure in the upstream region of PI-2b operon in all 26 ST17 genomes, which was absent in the 8 non-ST17 strains carrying the PI-2b locus. Deletion of this 43-bp sequence in strain BM110 resulted in a 3- to 5-fold increased transcription of PI-2b. Characterization of PI-2b promoter region in A909 and BM110 strains was carried out by RNAseq, primer extension, qRT-PCR and transcriptional fusions with gfp as reporter gene. Our results indicate the presence of a single promoter (Ppi2b) with a transcriptional start site (TSS) mapped 37 bases upstream of the start codon of the first PI-2b gene. The large operon of 16 genes located upstream of PI-2b codes for the group B carbohydrate (also known as antigen B), a major constituent of the bacterial cell wall. We showed that the hairpin sequence located between antigen B and PI-2b operons is a transcriptional terminator. In A909, increased expression of PI-2b probably results from read-through transcription from antigen B operon. In addition, we showed that an extended 5’ promoter region is required for maximal transcription of gfp as a reporter gene in S. agalactiae from Ppi2b promoter. Gene reporter assays performed in Lactococcus lactis strain NZ9000, a related non-pathogenic Gram-positive species, revealed that GBS-specific regulatory factors are required to drive PI-2b transcription. PI-2b expression is up-regulated in the BM110ΔcovR mutant as compared to the parental BM110 strain, but this effect is probably indirect

  6. DCS TERRAIN SUBMISSION FOR SHELBY COUNTY, TN

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Terrain data, as defined in FEMA Guidelines and Specifications, Appendix M: Data Capture Standards, describe the digital topographic data that were used to create...

  7. DCS Hydrology Submission for Shelby County OH

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydrology data include spatial datasets and data tables necessary for documenting the hydrologic procedures for estimating flood discharges for a flood insurance...

  8. 2006 MDEQ Camp Shelby, MS Lidar Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This metadata record describes the acquisition and processing of bare earth lidar data, raw point cloud lidar data, lidar intensity data, and floodmap breaklines...

  9. APPROXIMATE HYDRAULICS, SHELBY COUNTY,IA USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Recent developments in digital terrain and geospatial database management technology make it possible to protect this investment for existing and future projects to...

  10. A Decompositional Approach to Executing Quality Data Model Algorithms on the i2b2 Platform

    Science.gov (United States)

    Mo, Huan; Jiang, Guoqian; Pacheco, Jennifer A.; Kiefer, Richard; Rasmussen, Luke V.; Pathak, Jyotishman; Denny, Joshua C.; Thompson, William K.

    2016-01-01

    The Quality Data Model (QDM) is an established standard for representing electronic clinical quality measures on electronic health record (EHR) repositories. The Informatics for Integrated Biology and the Bedside (i2b2) is a widely used platform for implementing clinical data repositories. However, translation from QDM to i2b2 is challenging, since QDM allows for complex queries beyond the capability of single i2b2 messages. We have developed an approach to decompose complex QDM algorithms into workflows of single i2b2 messages, and execute them on the KNIME data analytics platform. Each workflow operation module is composed of parameter lists, a template for the i2b2 message, an mechanism to create parameter updates, and a web service call to i2b2. The communication between workflow modules relies on passing keys ofi2b2 result sets. As a demonstration of validity, we describe the implementation and execution of a type 2 diabetes mellitus phenotype algorithm against an i2b2 data repository. PMID:27570665

  11. Genetics Home Reference: RRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal ...

    Science.gov (United States)

    ... Munnich A, Rötig A. Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet. 2007 Jun;39(6):776-80. Epub 2007 May 7. Citation on PubMed GeneReview: RRM2B-Related Mitochondrial Disease Pontarin G, Ferraro P, Bee L, Reichard P, ...

  12. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2010

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2010 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  13. Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; de Wit, Heidi; Walter, Alexander M;

    2013-01-01

    is still high. We conclude that Doc2b acts to inhibit vesicle priming during prolonged calcium elevations, thus protecting unprimed vesicles from fusing prematurely, and redirecting them to refill the readily releasable pool after relaxation of the calcium signal. In sum, Doc2b favors fast, synchronized...

  14. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2009

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2009 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  15. Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations

    DEFF Research Database (Denmark)

    Urwin, Hazel; Authier, Astrid; Nielsen, Jørgen Erik

    2010-01-01

    Mutations in CHMP2B cause frontotemporal dementia (FTD) in a large Danish pedigree, which is termed FTD linked to chromosome 3 (FTD-3), and also in an unrelated familial FTD patient. CHMP2B is a component of the ESCRT-III complex, which is required for function of the multivesicular body (MVB), a...

  16. Fabrication Report for the AFC-2A and AFC-2B Capsule Irradiations in the ATR

    Energy Technology Data Exchange (ETDEWEB)

    Timothy A. Hyde

    2007-10-01

    This document provides a general narrative description of the AFC-2A and 2B fuel fabrication processes for the AFC 2A and AFC 2B fuel irradiation experiments fabricated at the Idaho National Laboratory’s Materials and Fuels Complex (MFC) for irradiation in the Advanced Test Reactor (ATR).

  17. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2011

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2011 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  18. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2012

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2012 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  19. 76 FR 3451 - Wage Methodology for the Temporary Non-agricultural Employment H-2B Program

    Science.gov (United States)

    2011-01-19

    ..., Refugees, Border Security, and International Law in April 2008, Ross Eisenbrey, Vice President of the...-2B Program: Hearing Before the Subcommittee on Immigration, Citizenship, Refugees, Border Security...- skill H-2B jobs causes an adverse effect because all workers in those job categories perform the same...

  20. Noncanonical sortase-mediated assembly of pilus type 2b in group B Streptococcus.

    Science.gov (United States)

    Lazzarin, Maddalena; Cozzi, Roberta; Malito, Enrico; Martinelli, Manuele; D'Onofrio, Mariapina; Maione, Domenico; Margarit, Immaculada; Rinaudo, C Daniela

    2015-11-01

    Group B Streptococcus (GBS) expresses 3 structurally distinct pilus types (1, 2a, and 2b) identified as important virulence factors and vaccine targets. These pili are heterotrimeric polymers, covalently assembled on the cell wall by sortase (Srt) enzymes. We investigated the pilus-2b biogenesis mechanism by using a multidisciplinary approach integrating genetic, biochemical, and structural studies to dissect the role of the 2 pilus-2b-associated Srts. We show that only 1 sortase (SrtC1-2b) is responsible for pilus protein polymerization, whereas the second one (Srt2-2b) does not act as a pilin polymerase, but similarly to the housekeeping class A Srt (SrtA), it is involved in cell-wall pilus anchoring by targeting the minor ancillary subunit. Based on its function and sequence features, Srt2-2b does not belong to class C Srts (SrtCs), nor is it a canonical member of any other known family of Srts. We also report the crystal structure of SrtC1-2b at 1.9 Å resolution. The overall fold resembles the typical structure of SrtCs except for the N-terminal lid region that appears in an open conformation displaced from the active site. Our findings reveal that GBS pilus type 2b biogenesis differs significantly from the current model of pilus assembly in gram-positive pathogens.

  1. Preparation and application of hydroxyapatite(HA) nanoparticles/NR2B-siRNA complex

    Institute of Scientific and Technical Information of China (English)

    YANG Hui; HUANG Dong; ZHU Shai-hong; YAN Xue-bin; GU Yong-hong; YAN Hui; WU Li-xiang

    2008-01-01

    Hydroxyapatite(HA) nanoparticles were prepared by coprecipitation-hydrothermal synthesis and their exosyndrome was estimated via transmission electron microscopy. Agarose gel electrophoresis and ultraviolet spectrophotometry were used to evaluate the ability of HA to bind NR2B-siRNA at different pH values and at different HA-NR2B-siRNA ratios. And the stability of the complex in saline was also evaluated. The effect of HA/NR2B-siRNA complex on chronic inflammatory pain was evaluated in vivo in mice. Transmission electron microscopy(TEM) reveals that HA nanoparticles are thin strips or short rod in shape and the one-dimensional particle size of HA nanoparticles is 40-50 nm. Under the acid or neutral condition, the Zeta potential of HA is positive; nanoparticles can completely bind NR2B-siRNA when the HA:NR2B-siRNA ratio is at or larger than 35-1; while under the alkaline condition, the affinity of HA to NR2B-siRNA is rather weak. HA/NR2B-siRNA complex is not dissociated when being resuspended in saline. The nociception of the tonic phase induced by formalin is significantly reduced in the HA/NR2B-siRNA treated mice as compared with the controls. Therefore, HA may be a new siRNA nano-vector material.

  2. SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

    Science.gov (United States)

    Sinai, Laleh; Duffy, Steven; Roder, John C.

    2010-01-01

    The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src…

  3. Data of evolutionary structure change: 1ANTI-2B4XL [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ANTI-2B4XL 1ANT 2B4X I L ---------RDIPMNPMCIYRSPEKKATNRRVWELSKANSRFATTFYQHLADSKNDNDNIFLSPLSISTAFAMTKLGACNDTLQQLMEVFKFDTISEKTSDQIHFFFAKLNCRLYRKANKSSKLVSANRLFGDKSLTFNETYQDISE...Chain> 1ANT I 1ANTI AASTA----VVIA...14> 1ANT I 1ANTI...ntryChain> 1ANT I 1ANTI

  4. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    Science.gov (United States)

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (penzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  5. First identification of Porcine Circovirus Type 2b mutant in pigs from Uruguay.

    Science.gov (United States)

    Ramos, Natalia; Mirazo, Santiago; Castro, Gustavo; Arbiza, Juan

    2015-07-01

    Porcine Circovirus Type 2 (PCV2) is a worldwide distributed virus and is considered an important emerging pathogen related to several distinct disease syndromes in pigs. PCV2 strains are classified into three genotypes: PCV2a, with five subtypes (2A-2E), PCV2b with three subtypes (1A-1C) and PCV2c, only found in Denmark. Recently, several reports suggested the circulation of newly emerging PCV2b mutants (mPCV2b) isolated from pigs with PCVAD in cases of suspected vaccine failure. In this work, we report for the first time the identification of mPCV2b in pigs from Uruguay, providing an additional evidence of a global circulation. Complete genome characterization and phylogenetic analysis reveal that Uruguayan strains, as well as mPCV2b previously reported are closely related to other sequences already classified as PCV2b-1C. Furthermore, results showed that mPCV2b presented different genetic markers in the capsid protein compared with classical PCV2a/b strains. Further investigation about antigenic shift of the mPCV2b strains including the Uruguayan isolates is needed.

  6. Data of evolutionary structure change: 2B9RA-2BPMD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 2B9RA-2BPMD 2B9R 2BPM A D -VKDIYAYLRQLEAAQAVRPKYLLGR-EVTGNMRAILID...line>THR CA 261 GLY CA 332 ASN CA 307 2BPM... D 2BPMD YMKKQPDITNS .../line> ASP CA 206 VAL CA 247 GLU CA 298 2BPM... D 2BPMD

  7. Data of evolutionary structure change: 1BEDA-2B6MA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BEDA-2B6MA 1BED 2B6M A A AQFKEGEHYQVLKTPASSSPVVSEFFSFYCPHCNTF---...HHHHHHHHHH EEEE EEEEE HHHHHHHHHHHHHH - 0 1BED... A 1BEDA HCNTF---E...e> ALA CA 306 SER CA 272 1BED... A 1BEDA HTLRKPPKDEQ

  8. XO-2b: a Prograde Planet with a Negligible Eccentricity, and an Additional Radial Velocity Variation

    CERN Document Server

    Narita, Norio; Sato, Bun'ei; Harakawa, Hiroki; Fukui, Akihiko; Aoki, Wako; Tamura, Motohide

    2011-01-01

    We present precise radial velocities of XO-2 taken with the Subaru HDS, covering two transits of XO-2b with an interval of nearly two years. The data suggest that the orbital eccentricity of XO-2b is consistent with zero within 2$\\sigma$ ($e=0.045\\pm0.024$) and the orbit of XO-2b is prograde (the sky-projected spin-orbit alignment angle $\\lambda=10^{\\circ}\\pm72^{\\circ}$). The poor constraint of $\\lambda$ is due to a small impact parameter (the orbital inclination of XO-2b is almost 90$^{\\circ}$). The data also provide an improved estimate of the mass of XO-2b as $0.62\\pm0.02$ $M_{\\rm Jup}$. We also find a long-term radial velocity variation in this system. Further radial velocity measurements are necessary to specify the cause of this additional variation.

  9. Global view of transcriptome in the brains of aged NR2B transgenic mice*****

    Institute of Scientific and Technical Information of China (English)

    Chunxia Li; Men Su; Huimin Wang; Yinghe Hu

    2013-01-01

    NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as wel as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.

  10. Interferon-alpha-2b induces autophagy in hepatocellular carcinoma cells through Beclin1 pathway

    Institute of Scientific and Technical Information of China (English)

    Jun Zhao; Ming-Li Wang; Zeng Li; Dong-Mei Gao; Yu Cai; Jun Chang; Shi-Ping Wang

    2014-01-01

    Objective:To determine whether Interferon-alpha-2b (IFN-α2b) can modulate the autophagic response in hepatocellular carcinoma cells. Methods:Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission electron microscopy and immunoblotting. Results:Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. hTe acridine orange HepG2 cell ratios were (4.3±1.0)%, (6.9±1.4)%, and (13.1±2.3)%, respectively, atfer treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punctate pattern was observed in HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h, but only diffuse and weakly lfuorescent GFP-LC3 puncta was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like characteristics, including single-or double-membrane vacuoles containing intact and degraded cellular debris. The Beclin1 and LC3-II protein expression was up-regulated by IFN-α2b treatment. Conclusion:Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclin1 signaling pathway was stimulated by IFN-α2b.

  11. RET(MEN 2B) is active in the endoplasmic reticulum before reaching the cell surface.

    Science.gov (United States)

    Runeberg-Roos, P; Virtanen, H; Saarma, M

    2007-12-13

    MEN 2B (multiple endocrine neoplasia type 2B) is an autosomal dominant cancer syndrome caused by an oncogenic form of the receptor tyrosine kinase REarranged during transfection (RET). The MEN 2B syndrome is associated with an abnormal autophosphorylation of the mutated receptor even without ligand-stimulation. Here, we characterize the activation of a RET(MEN 2B) variant carrying the point mutation Met918Thr, and show that the 150 kDa precursor of RET(MEN 2B) becomes phosphorylated already during synthesis in the endoplasmic reticulum (ER). At least three different tyrosine residues (Tyr905, Tyr1062, Tyr1096) of the RET(MEN 2B) precursor are phosphorylated before the oncogenic receptor reaches the cell surface. We also demonstrate that the precursor of RET(MEN 2B) interacts with both growth factor receptor-bound protein and Src homology 2 domain-containing already in the ER, and that this interaction is dependent on the kinase activity of RET. With the aid of two RET mutants (RET(MEN 2B/S32L) and RET(MEN 2B/F393L)), which accumulate in the ER, we show that the oncogenic precursor of the receptor has the capacity to activate AKT, extracellular signal-regulated kinase and signal transducer and activator of transcription 3 from the ER. Taken together, our data demonstrate that the oncogenic precursor of RET(MEN 2B) is phosphorylated, interacts with adapter proteins and induces downstream signalling from the ER.

  12. Cytochrome P450 2B diversity and dietary novelty in the herbivorous, desert woodrat (Neotoma lepida).

    Science.gov (United States)

    Malenke, Jael R; Magnanou, Elodie; Thomas, Kirk; Dearing, M Denise

    2012-01-01

    Detoxification enzymes play a key role in plant-herbivore interactions, contributing to the on-going evolution of ecosystem functional diversity. Mammalian detoxification systems have been well studied by the medical and pharmacological industries to understand human drug metabolism; however, little is known of the mechanisms employed by wild herbivores to metabolize toxic plant secondary compounds. Using a wild rodent herbivore, the desert woodrat (Neotoma lepida), we investigated genomic structural variation, sequence variability, and expression patterns in a multigene subfamily involved in xenobiotic metabolism, cytochrome P450 2B (CYP2B). We hypothesized that differences in CYP2B expression and sequence diversity could explain differential abilities of woodrat populations to consume native plant toxins. Woodrats from two distinct populations were fed diets supplemented with either juniper (Juniperus osteosperma) or creosote bush (Larrea tridentata), plants consumed by woodrats in their respective desert habitats. We used Southern blot and quantitative PCR to determine that the genomic copy number of CYP2B in both populations was equivalent, and similar in number to known rodent copy number. We compared CYP2B expression patterns and sequence diversity using cloned hepatic CYP2B cDNA. The resulting sequences were very diverse, and clustered into four major clades by amino acid similarity. Sequences from the experimental treatments were distributed non-randomly across a CYP2B tree, indicating unique expression patterns from woodrats on different diets and from different habitats. Furthermore, within each major CYP2B clade, sequences shared a unique combination of amino acid residues at 13 sites throughout the protein known to be important for CYP2B enzyme function, implying differences in the function of each major CYP2B variant. This work is the most comprehensive investigation of the genetic diversity of a detoxification enzyme subfamily in a wild mammalian

  13. Cytochrome P450 2B diversity and dietary novelty in the herbivorous, desert woodrat (Neotoma lepida.

    Directory of Open Access Journals (Sweden)

    Jael R Malenke

    Full Text Available Detoxification enzymes play a key role in plant-herbivore interactions, contributing to the on-going evolution of ecosystem functional diversity. Mammalian detoxification systems have been well studied by the medical and pharmacological industries to understand human drug metabolism; however, little is known of the mechanisms employed by wild herbivores to metabolize toxic plant secondary compounds. Using a wild rodent herbivore, the desert woodrat (Neotoma lepida, we investigated genomic structural variation, sequence variability, and expression patterns in a multigene subfamily involved in xenobiotic metabolism, cytochrome P450 2B (CYP2B. We hypothesized that differences in CYP2B expression and sequence diversity could explain differential abilities of woodrat populations to consume native plant toxins. Woodrats from two distinct populations were fed diets supplemented with either juniper (Juniperus osteosperma or creosote bush (Larrea tridentata, plants consumed by woodrats in their respective desert habitats. We used Southern blot and quantitative PCR to determine that the genomic copy number of CYP2B in both populations was equivalent, and similar in number to known rodent copy number. We compared CYP2B expression patterns and sequence diversity using cloned hepatic CYP2B cDNA. The resulting sequences were very diverse, and clustered into four major clades by amino acid similarity. Sequences from the experimental treatments were distributed non-randomly across a CYP2B tree, indicating unique expression patterns from woodrats on different diets and from different habitats. Furthermore, within each major CYP2B clade, sequences shared a unique combination of amino acid residues at 13 sites throughout the protein known to be important for CYP2B enzyme function, implying differences in the function of each major CYP2B variant. This work is the most comprehensive investigation of the genetic diversity of a detoxification enzyme subfamily in a

  14. Characterization of the A2B adenosine receptor from mouse, rabbit, and dog.

    Science.gov (United States)

    Auchampach, John A; Kreckler, Laura M; Wan, Tina C; Maas, Jason E; van der Hoeven, Dharini; Gizewski, Elizabeth; Narayanan, Jayashree; Maas, Garren E

    2009-04-01

    We have cloned and pharmacologically characterized the A(2B) adenosine receptor (AR) from the dog, rabbit, and mouse. The full coding regions of the dog and mouse A(2B)AR were obtained by reverse transcriptase-polymerase chain reaction, and the rabbit A(2B)AR cDNA was obtained by screening a rabbit brain cDNA library. It is noteworthy that an additional clone was isolated by library screening that was identical in sequence to the full-length rabbit A(2B)AR, with the exception of a 27-base pair deletion in the region encoding amino acids 103 to 111 (A(2B)AR(103-111)). This 9 amino acid deletion is located in the second intracellular loop at the only known splice junction of the A(2B)AR and seems to result from the use of an additional 5' donor site found in the rabbit and dog but not in the human, rat, or mouse sequences. [(3)H]3-Isobutyl-8-pyrrolidinoxanthine and 8-[4-[((4-cyano-[2,6-(3)H]-phenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl)xanthine ([(3)H]MRS 1754) bound with high affinity to membranes prepared from human embryonic kidney (HEK) 293 cells expressing mouse, rabbit, and dog A(2B)ARs. Competition binding studies performed with a panel of agonist (adenosine and 2-amino-3,5-dicyano-4-phenylpyridine analogs) and antagonist ligands identified similar potency orders for the A(2B)AR orthologs, although most xanthine antagonists displayed lower binding affinity for the dog A(2B)AR compared with A(2B)ARs from rabbit and mouse. No specific binding could be detected with membranes prepared from HEK 293 cells expressing the rabbit A(2B)AR(103-111) variant. Furthermore, the variant failed to stimulate adenylyl cyclase or calcium mobilization. We conclude that significant differences in antagonist pharmacology of the A(2B)AR exist between species and that some species express nonfunctional variants of the A(2B)AR due to "leaky" splicing.

  15. Neutron diffraction studies of magnetic ordering in superconducting ErNi2B2C and TmNi2B2C in an applied magnetic field

    DEFF Research Database (Denmark)

    Toft, Katrine Nørgaard

    along [110], the magnetic structure rotates a small angle of 0.5 degrees away from the symmetrydirection. TmNi2B2C: A magnetic field applied in the [100] direction suppresses the zero field magnetic structure QF = (0.094,0.094,0) (TN = 1.6 K), in favor of the Fermi surface nesting structure QN = (0......The field-induced magnetic structures of ErNi2B2C and TmNi2B2C in are especially interesting because the field suppresses the superconducting order parameter and therefore the magnetic properties can be studied while varying the strength ofsuperconductivity. ErNi2B2C: For magnetic fields along all...... three symmetry directions, the observed magnetic structures have a period corresponding to the Fermi surface nesting structure. The phase diagrams present all the observed magnetic structures.Two results remain unresolved: 1. When applying the magnetic field along [010], the minority domain (QNB = (0,Q...

  16. Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Michael R Kraus; Arne Sch(a)fer; Herbert Csef; Michael Scheurlen

    2005-01-01

    AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon.METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μgpeginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R).RESULTS: Therapy with pegylated interferon alfa-2bproduces comparable scores for depression (ANOVA:P = 0.875) as compared to conventional interferon.Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups.CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.

  17. Unconventional morphologies in ordered melts of symmetric multiblock copolymers A(mN/2)(B(N/2)A(N/2))B-mN/2

    NARCIS (Netherlands)

    Smirnova, YG; ten Brinke, G; Erukhimovich, IY

    2005-01-01

    In the limit of weak segregation, microphase separation in melts of symmetric multiblock copolymers with the structural formula A(mN/2)(B(N/2)A(N/2))(n)B-mN/2 was theoretically analyzed. It was shown for the first time that, in the case of these two-length-scale block copolymers AB, competition betw

  18. Differential role of SH2-B and APS in regulating energy and glucose homeostasis.

    Science.gov (United States)

    Li, Minghua; Ren, Decheng; Iseki, Masanori; Takaki, Satoshi; Rui, Liangyou

    2006-05-01

    SH2-B and APS, two members of a pleckstrin homology and SH2 domain-containing adaptor family, promote both insulin and leptin signaling in a similar fashion in cultured cells. In addition, APS mediates insulin-stimulated activation of the c-Cbl/CAP/TC10 pathway in cultured adipocytes. Here we characterized genetically modified mice lacking SH2-B, APS, or both to determine the physiological roles of these two proteins in animals. Disruption of the SH2-B gene resulted in obesity, hyperglycemia, hyperinsulinemia, and glucose intolerance. Conversely, deletion of the APS gene did not alter adiposity, energy balance, and glucose metabolism. Energy intake, energy expenditure, fat content, body weight, and plasma insulin, leptin, glucose, and lipid levels were similar between APS(-/-) and WT littermates fed either normal chow or a high-fat diet. Moreover, deletion of APS failed to alter insulin and glucose tolerance. APS(-/-)/SH2-B(-/-) double knockout mice also developed energy imbalance, obesity, hyperleptinemia, hyperinsulinemia, hyperglycemia, and glucose intolerance; however, plasma leptin and insulin levels were significantly lower in APS(-/-)/SH2-B(-/-) than in SH2-B(-/-) mice. These results suggest that SH2-B, but not APS, is a key positive regulator of energy and glucose metabolism in mice.

  19. Structural characterization and antiviral effect of a novel polysaccharide PSP-2B from Prunellae Spica.

    Science.gov (United States)

    Ma, Feng-Wei; Kong, Si-Yuan; Tan, Hong-Sheng; Wu, Rong; Xia, Bing; Zhou, Yan; Xu, Hong-Xi

    2016-11-05

    In the present study, a novel polysaccharide, PSP-2B, was isolated from aqueous extracts of Prunellae Spica by direct ultrafiltration membrane separation and gel chromatography purification. PSP-2B is a partially sulphated polysaccharide with a molecular weight of approximately 32kDa. Its sulfate content is 10.59% by elemental analysis. The major sugars comprising PSP-2B are arabinose, galactose and mannose, in addition to small amounts of glucose and uronic acids. The framework of PSP-2B is speculated to be a branched arabinogalactomannan, and the side chains are terminated primarily by the Araf residues. PSP-2B also contains 2.98% protein. PSP-2B exhibits activity against herpes simplex virus (HSV), with a half maximal inhibitory concentration (IC50) of approximately 69μg/mL for HSV-1 and 49μg/mL for HSV-2. However, PSP-2B demonstrated no cytotoxicity even when its concentration was increased to 1600μg/mL, suggesting that it has potential as an anti-HSV drug candidate.

  20. The influence of VO2(B nanobelts on thermal decomposition of ammonium perchlorate

    Directory of Open Access Journals (Sweden)

    Zhang Yifu

    2015-09-01

    Full Text Available The influence of vanadium dioxide VO2(B on thermal decomposition of ammonium perchlorate (AP has not been reported before. In this contribution, the effect of VO2(B nanobelts on the thermal decomposition of AP was investigated by the Thermo- Gravimetric Analysis and Differential Thermal Analysis (TG/DTA. VO2(B nanobelts were hydrothermally prepared using peroxovanadium (V complexes, ethanol and water as starting materials. The thermal decomposition temperatures of AP in the presence of I wt.%, 3 wt.% and 6 wt.% of as-obtained VO2<B nanobelts were reduced by 39 °C. 62 °C and 74 °C, respectively. The results indicated that VO2(B nanobelts had a great influence on the thermal decomposition temperature of AP Furthermore, the influence of the corresponding V2Os, which was obtained by thermal treatment of VO2(B nanobelts, on the thermal decomposition of AP was also investigated. The resufs showed that VO2(B nanobelts had a greater influence on the thermal decomposition temperature of AP than that of V2Os.

  1. A functional variant in the UBE2B gene promoter is associated with idiopathic azoospermia.

    Science.gov (United States)

    Mou, Lisha; Zhang, Qiang; Diao, Ruiying; Cai, Zhiming; Gui, Yaoting

    2015-07-30

    A variety of genetic variants lead to abnormal human spermatogenesis. The ubiquitin-conjugating enzyme E2B (UBE2B) plays a significant role in spermatogenesis as Ube2b-knockout male mice are infertile. In this study, we sequenced the exon and promoter region of UBE2B in 776 patients diagnosed with idiopathic azoospermia (IA) and 709 proven fertile men to examine whether UBE2B is involved in the pathogenesis of IA. In the exon region, two novel synonymous variants were detected in the patient group. In the promoter region, four known variants and four novel variants were identified in the patient group. Of the novel variants in the promoter region, three were located at the binding site of specificity protein 1 (SP1) transcription factor analyzed by TRANSFAC software. Luciferase assays demonstrated that one heterozygous variant (Chr5.133706925 A > G) inhibited the transcriptional regulation activity of SP1. A novel variant (Chr5.133706925 A > G) residing in the UBE2B gene promoter region confers a high risk for IA in a Chinese population. These results support a role for UBE2B in the pathogenesis of IA.

  2. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease.

    Science.gov (United States)

    Karmouty-Quintana, Harry; Zhong, Hongyan; Acero, Luis; Weng, Tingting; Melicoff, Ernestina; West, James D; Hemnes, Anna; Grenz, Almut; Eltzschig, Holger K; Blackwell, Timothy S; Xia, Yang; Johnston, Richard A; Zeng, Dewan; Belardinelli, Luiz; Blackburn, Michael R

    2012-06-01

    Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A(2B)R activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A(2B)R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease.

  3. 3D-QSAR studies on UDP-glucuronosyltransferase 2B7 substrates using the pharmacophore and VolSurf approaches.

    Science.gov (United States)

    Ako, Roland; Dong, Dong; Wu, Baojian

    2012-09-01

    UDP-glucuronosyltransferase 2B7 (UGT2B7) is an important enzyme responsible for clearance of many drugs. Here, we report two 3D quantitative structure-activity relationship (QSAR) models for UGT2B7 using the pharmacophore and VolSurf approach, respectively. The dataset included 53 structurally diverse UGT2B7 substrates, 36 of which were used for the training set and 17 of which for the external test set. Pharmacophore-based 3D-QSAR model (or hypothesis) was developed using the Discovery Studio program. A user-defined "glucuronidation site" feature was forcefully included in a pharmacophore hypothesis. VolSurf-based 3D-QSAR model was generated using the VolSurf program. This involves calculation of VolSurf descriptors, variable selection with the FFD algorithm, and partial least squares (PLS) analyses. The best pharmacophore model (r(2) = 0.736) consists of one glucuronidation site, one hydrogen bond acceptor, and three hydrophobic regions. Using this model, K(m) values for 14 of 17 test substrates were predicted within one log unit. The yielded VolSurf (PLS) model with two components shows statistical significance in both fitting and internal predicting (r(2) = 0.866, q(2) = 0.728). Further, the K(m) values for all test substrates were predicted within one log unit. In addition, the VolSurf model reveals an overlay of chemical features influencing the enzyme-substrate binding. Those include molecular size and shape, integy moments, capacity factors, best volumes of DRY probe, H-bonding, and log P. In conclusion, the pharmacophore and VolSurf approaches are successfully utilized to establish predictive models for UGT2B7. The derived models should be an efficient tool for high throughput prediction of UGT2B7 metabolism.

  4. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    Science.gov (United States)

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2.

  5. Using service design methods for B2b service brand concept development: Case company

    OpenAIRE

    Molina Escalante, Hugo

    2014-01-01

    A short time before this study was initiated, a small B2b service company had just began op-erating its business without a brand of it’s own. The company owners were looking to design an innovative brand for their business. The purpose of this thesis was to develop the brand for this service Company in the B2b context, using practical service design and Strategic design research methods. This thesis report represents a framework for developing a B2b service brand using research methods c...

  6. An Empirical Examination of Reverse Auction Appropriateness in B2B Source Selection

    Science.gov (United States)

    2006-01-01

    Measures of Marketing Constructs," Journal of Marketing Research, Vol. 16, No.2, pp. 64 - 73. Cohn, L. (2000), " B2B : The Hottest Net Bet Yet...AND SUBTITLE 5. FUNDING NUMBERS AN EMPIRICAL EXAMINATION OF REVERSE AUCTION APPROPRIATENESS IN B2B SOURCE SELECTION. 6. AUTHOR(S) MAJ HAWKINS TIMOTHY...Examination of Reverse Auction Appropriateness in B2B Source Selection D :7;TZU IUT•ITM STATER,;77TIT A Approved for Puhtic P-•-!,ase Distribution

  7. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

    2008-01-01

    chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  8. I2B is a small cytosolic protein that participates in vacuole fusion

    OpenAIRE

    1997-01-01

    Saccharomyces cerevisiae vacuole inheritance requires two low molecular weight activities, LMA1 and LMA2. LMA1 is a heterodimer of thioredoxin and protease B inhibitor 2 (I2B). Here we show that the second low molecular weight activity (LMA2) is monomeric I2B. Though LMA2/I2B was initially identified as a protease B inhibitor, this protease inhibitor activity is not related to its ability to promote vacuole fusion: (i) Low Mr protease B inhibitors cannot substitute for LMA1 or LMA 2, (ii) LMA...

  9. The U2B'' RNP motif as a site of protein-protein interaction.

    OpenAIRE

    Scherly, D; Dathan, N A; Boelens, W; van Venrooij, W J; Mattaj, I W

    1990-01-01

    The U2 snRNP contains two specific proteins, U2B'' and U2A'. Neither of these proteins, on its own, is capable of specific interactions with U2 RNA. Here, a complex between U2B'' and U2A' that forms in the absence of RNA is identified. Analysis of mutant forms of U2B'' shows that the smallest fragment able to bind specifically U2 RNA (amino acids 1-88) is also the minimal region required for complex formation with U2A', and implies that this region must be largely structurally intact for U2A'...

  10. Project Description Advanced Fuel Cycle Initiative AFC-2A and AFC-2B Experiments

    Energy Technology Data Exchange (ETDEWEB)

    AFCI AFC-2A and AFC-2B Experiments Project Executi

    2007-03-01

    The proposed AFC-2A and AFC-2B irradiation experiments are a continuation of the AFC-1 fuel test series currently in progress in the ATR. This document discusses the experiments and the planned activities that will take place.

  11. High performance of solvothermally prepared VO2(B as anode for aqueous rechargeable lithium batteries

    Directory of Open Access Journals (Sweden)

    Milošević Sanja

    2015-01-01

    Full Text Available The VO2 (B was synthesized via a simple solvothermal route at 160oC in ethanol. The initial discharge capacity of VO2 (B anode, in saturated aqueous solution of LiNO3, was 177 mAh g-1 at a current rate of 50 mA g-1. After 50 cycles capacity fade was 4%, but from 20th-50th cycle no capacity drop was observed. The VO2 (B has shown very good cyclability at current rate of even 1000 mA g-1 with initial discharge capacity of 92 mAh g-1. The excellent electrochemical performance of VO2 (B was attributed to the stability of micro-nano structures to repeated intercalation /deintercalation process, very good electronic conductivity as well as the very low charge transfer resistance in the aqueous electrolyte. [Projekat Ministarstva nauke Republike Srbije, br. III45014

  12. Managing Innovation Through Social Media in B2B SME-Context

    DEFF Research Database (Denmark)

    Lutz, Salla; Madsen, Svend Ole; Brink, Tove

    2015-01-01

    This paper shed light on how social media application can enhance innovation management in SME B2B context. Our study employs a qualitative case study approach with four B2B SMEs for in-depth research in the period from October 2013 to October 2014. The B2B SME managers aim for open business model...... innovation. However, social media application is hindered due to lack of specific local knowledge, lack of knowledge on social media technicalities and bewilderedness on leadership approaches within the social media application. A contribution is hereby made to the B2B SME field, to the academic...... understanding an insight on social media application and open business model innovation....

  13. Data of evolutionary structure change: 1DJ2B-1ADIA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DJ2B-1ADIA 1DJ2 1ADI B A IGSLSQVSGVLGCQWGDEGKGKLVDILAQHFDIVARCQG...LLSEACPLILDYHVALDNAREKARGAKAIGTTGRGIGPAYEDKVARRGLRVGDLFDKETFAEKLKEVMEYHNFQLVNYYKAEAVDYQKVLDDTMAVADI...5 PHE CA 263 LYS CA 227 TYR CA 251 1ADI... A 1ADIA 1 1ADI A 1ADI

  14. Targeted Deletion of Titin N2B Region Leads to Diastolic Dysfunction and Cardiac Atrophy

    National Research Council Canada - National Science Library

    Michael H. Radke; Jun Peng; Yiming Wu; Mark McNabb; O. Lynne Nelson; Henk Granzier; Michael Gotthardt

    2007-01-01

    .... Cardiac titin contains a unique N2B region, which has been proposed to modulate elasticity of the titin filament and to be important for hypertrophy signaling and the ischemic stress response through...

  15. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2014

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Crane Creek are described in this report. Water-Data Report 2013 413721083124001 Pool 2B at Ottawa NWR...

  16. Data of evolutionary structure change: 1AW2B-2VENA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AW2B-2VENA 1AW2 2VEN B A --RHPVVMGNWKLNGSKEMVVDLLNGLNAELEGVTGVDV...RQLDAVINTQGVEALEGAIIAYEPIWAIGTGKAATAEDAQRIHAQIRAHIAEK-SEAVAKNVVIQYGGSVKPENAAAYFAQPDIDGALVGGAALDAKSFAAIAKAAAE...ine> 2VEN A 2VENA1 2VEN A 2VENA... A 2VENA YEPVW-----KVATP

  17. B2B SME Management of Antecedents to the Application of Social Media

    DEFF Research Database (Denmark)

    Brink, Tove

    2017-01-01

    2013 to October 2014, with follow-up interviews in October 2015. The findings reveal two important antecedents to the application of social media that overcome the gap between acknowledging the usefulness of social media and its actual limited application in practical B2B contexts. First, open...... application stages and the gaps between them identified in the previous literature. The developed model makes a contribution to the B2B SME field and to academia by recognising the importance of integrating critical antecedents before social media application can enhance business in B2B SMEs......This paper elucidates how business-to-business (B2B) small and medium-sized enterprises (SMEs) can manage antecedents to the application of social media for potential contributions to their business. This in-depth qualitative research study was conducted at four plastic-producing SMEs from October...

  18. Thermoluminescence characteristics of gamma irradiated Li2B4O7:Cu nanophosphor

    Science.gov (United States)

    Chopra, Vibha; Singh, Lakhwant; Lochab, S. P.

    2013-07-01

    Nanocrystals of the Li2B4O7:Cu were synthesized by the combustion method using different concentrations of Cu. X-ray diffraction (XRD) spectra and transmission electron microscopy (TEM) image confirm the nanometric size of synthesized material. The thermal stability of phosphor was obtained by thermogravimetric analysis (TGA). TL characteristics of the synthesized Li2B4O7:Cu material doped with Cu of concentrations 1000 ppm and 2500 ppm were studied. It is observed that Li2B4O7:Cu doped with Cu (both 1000 ppm and 2500 ppm) exhibit a linear response in the range 1×100-5×103 Gy of gamma radiations. Finally the trapping parameters associated with the glow peaks were calculated using the glow curve deconvolution (GCD) glow fit method. Fading and reproducibility of phosphors were also studied and it was found that the Li2B4O7:Cu is quite suitable for radiation dosimetry.

  19. Boriding kinetics of Fe2B layers formed on AISI 1045 steel

    Directory of Open Access Journals (Sweden)

    Zuno-Silva J.

    2014-01-01

    Full Text Available In the present work, a diffusion model was suggested to study the growth kinetics of Fe2B layers grown on the AISI 1045 steel by the pack-boriding treatment. The generated boride layers were analyzed by optical microscopy and X-ray diffraction analysis. The applied diffusion model is based on the principle of mass conservation at the (Fe2B/ substrate interface. It was used to estimate the boron diffusion coefficients of Fe2B in the temperature range of 1123-1273 K. A validation of the model was also made by comparing the experimental Fe2B layer thickness obtained at 1253 K for 5 h of treatment with the predicted value. Basing on our experimental results, the boron activation energy was estimated as 180 kJ mol-1 for the AISI 1045 steel.

  20. A simple method for quantification of interferon-α2b through surface ...

    African Journals Online (AJOL)

    USER

    2010-03-15

    Mar 15, 2010 ... 2Department of Process and Food Engineering, Faculty of ... interferon-α2b and anti-interferon monoclonal antibody was predominantly controlled by mass transfer ..... resonance characterization of drug/liposome interactions.

  1. Data of evolutionary structure change: 3EK2B-3FNFB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 6833343506 EVID> 3 3FNF EVID> 4 3FNF B 3FNF...EVID>EVID> 5 3FNF...3EK2B-3FNFB 3EK2 3FNF B B MGFLDGKRILLTGLLSNRSIAYGIAKACKREGAELAFTY...VGDRFKDRITEFAAEFGSE-LVFPCDVADDAQIDALFASLKTHWD---SLDGLVHSIGFAPREAIAG-DFLDGLTRENFRIAHDISAYSFPALAKAALPMLSDDASLL

  2. High-performance lithium storage based on the synergy of atomic-thickness nanosheets of TiO2(B) and ultrafine Co3O4 nanoparticles

    Science.gov (United States)

    Mujtaba, Jawayria; Sun, Hongyu; Zhao, Yanyan; Xiang, Guolei; Xu, Shengming; Zhu, Jing

    2017-09-01

    Lithium ion batteries (LIBs) are critical constituents of modern day vehicular and telecommunication technologies. Transition metal oxides and their composites have been extensively studied as potential electrode materials for LIBs. However, inefficient lithiation, poor electrical conductivity, and drastic volume change during cycling result in low reversible capacity and rapid capacity fading, and thus hinder the practical applications of those electrodes. In this work, we report a facile synthesis of a novel hierarchical composites, which consist of ultrafine Co3O4 nanoparticles uniformly dispersed on TiO2(B) nanosheets with atomic thickness (Co3O4 NPs@TiO2(B) NSs). When tested as anode material for LIBs, the Co3O4 NPs@TiO2(B) NSs sample with optimized composition shows a reversible capacity of ∼677.3 mAhg-1 after 80 cycles at a current density of 100 mAg-1. A capacity of 386.2 mAhg-1 is still achieved at 1000 mAg-1. The synergistic effect of ultrafine Co3O4 nanoparticles and atomic-thickness TiO2(B) nanosheets is responsible for the enhanced electrochemical performance.

  3. Drivers of relationships affecting B2B firms in an e-commerce environment

    Directory of Open Access Journals (Sweden)

    Irene Samanta

    2014-09-01

    Full Text Available The advent of the internet has created numerous opportunities for B2B marketing professionals to enhance current marketing practices, including electronic relationships. However, the investigation of e-relationships and the factors that influence e-relationships in an internet environment is scant. Further, there appears to be no investigation of this phenomenon within the context of Greek B2B Medium-sized firms (MSF. Τhe research problem investigated in this research is: “Which drivers in B2B e-commerce use affect inter-firm relationships in medium-sized B2B firms?”. A framework for B2B e-commerce relationships in a changing and globalized environment was synthesised and integrated with the literature about relationship marketing to arrive at the following research issues: “How do relationship marketing drivers affect the management of B2B e-relationships?”. An explanatory quantitative research approach was used and quantitative data was collected from B2B firms in Greece, which represents a case of e-commerce progress during the last six years. Regarding social exchange, some important differences emerge where cooperation between B2B e-commerce firms is concerned. Suppliers engaged in electronic commerce are more committed and oriented to a long-term relationship than buyers, based on both previous and current experience with them. Confidence in the relationships, consistency and honesty with their obligations and the exchange of reliable, trustworthy information and advisory services between firms are important factors in the development and establishment of their e-relationships. The main contribution of this research is the development of a theoretical framework for e-relationships in medium-sized Β2Β firms. That framework is the first rigorously researched step towards understanding the importance of these powerful streams of relationship drivers in total, and the business activity of e-marketing and electronic relationships.

  4. Framing agenda for business model innovation research from the B2B context

    OpenAIRE

    Neupane, Ganesh Prasad; Haugland, Sven A.

    2016-01-01

    This paper reviews the literature on business models in the business-to-business (B2B) context and proposes a research agenda that can be explored by future studies using various management and organizational theories. We outline four research themes and seven research topics for research on business model innovations in the B2B context. Further studies on these topics can make significant contributions to the business model literature.

  5. An analysis of Common Missile and TOW 2B using the Janus combat simulation

    OpenAIRE

    2002-01-01

    Approved for public release; distribution is unlimited. The US Army is currently developing a new close combat missile system, Common Missile, to replace the aging Tubelaunched, Optically-tracked, Wire-guided (TOW 2B) and HELLFIRE missile systems. The Common Missile will have a greater range and improved target acquisition capability over the current missile systems. The purpose of this thesis is to compare the performance of the Common Missile and the TOW 2B missile in a simulated ground ...

  6. Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein.

    Directory of Open Access Journals (Sweden)

    Da Ao

    Full Text Available Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER, with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+ concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.

  7. Diagnostic and therapeutic approach to multiple endocrine neoplasia type 2B in pediatric patients.

    Science.gov (United States)

    Torre, M; Martucciello, G; Ceccherini, I; Lerone, M; Aicardi, M; Gambini, C; Jasonni, V

    2002-09-01

    Multiple endocrine neoplasia (MEN) 2B is a hereditary syndrome including medullary thyroid carcinoma (MTC), pheochromocytoma, gastrointestinal (GI) disorders, marfanoid facies, and multiple ganglioneuromas. MTC is the major cause of mortality, and often appears during the 1st decade of life. RET proto-oncogene mutations are responsible for MEN 2B. Other RET mutations cause MEN 2A syndrome, familial MTC, or Hirschsprung's disease. We studied three MEN 2B patients with the aim of delineating the best diagnostic and therapeutic protocol. The gold standards for diagnosis are histochemical study of the rectal mucosa and molecular analysis of RET, which in familial cases detects MEN 2B at a preclinical stage so that early total prophylactic thyroidectomy can be performed. In non-familial cases, the diagnosis can be suggested by the presence of GI symptoms, ganglioneuromas, and/or the typical facies. The intestinal innervation pattern, analyzed with the acetylcholinesterase technique, is pathognomonic for MEN 2B. In our protocol a rectal biopsy is, therefore, the first measure. The surgical treatment of MEN 2B is total thyroidectomy with cervical lymphadenectomy of the central compartment of the neck. When possible, this intervention should be performed prophylactically before 1 year of age.

  8. [Prooxidant and cytotoxic action of N-acetylcysteine and glutathione combined with vitamin Bl2b].

    Science.gov (United States)

    Solov'eva, M E; Solov'ev, V V; Faskhutdinova, A A; Kudriavtsev, A A; Akatov, V S

    2007-01-01

    We studied the prooxidant and cytotoxic action of thiols N-acetylcystein (NAC) and glutathione (GSH) combined with vitamin Bl2b. The synergism of action of the thiols and Bl2b resulted in human carcinoma cell damage was found. It was shown that GSH and NAC in physiological doses combined with Bl2b caused the initiation of apoptosis. It was established that prooxidant action of the thiols combined with vitamin Bl2b, i. e. generation and accumulation of hydrogen peroxide in culture medium, led to intracellular oxidative stress and injury of cell redox system. These effects were completely abolished by nonthiol antioxidants catalase and pyruvate. The chelators of iron phenanthroline and deferoxamine did not suppress the H2O2 accumulation in culture medium but significantly inhibited the cell death induced by the thiols combined with Bl2b. Therefore, the thiols GSH and NAC widely used as antioxidants, in combination with vitamin Bl2b show prooxidant characteristics and induce, with the participation of intracellular iron, apoptotic HEp-2 cell death.

  9. Sperm nuclear histone H2B: correlation with sperm DNA denaturation and DNA stainability

    Institute of Scientific and Technical Information of China (English)

    Armand Zini; Xiaoyang Zhang; Maria San Gabriel

    2008-01-01

    Aim: To examine the relationship between sperm DNA damage and sperm nuclear histone (H2B) staining. Methods:We evaluated sperm samples from 14 consecutive asthenoteratozoospermic infertile men and six consecutive fertile controls. Sperm nuclear histone (H2B) staining and sperm chromatin integrity (assessed by sperm chromatin structure assay and expressed using the percentage of (I) DNA fragmentation index [%DFI] and (ii) high DNA stainability [%HDS)]) were evaluated. Results: Histone H2B immunocytochemistry demonstrated two nuclear staining patterns: (I) focal punctate staining; and (ii) diffuse staining. Infertile men had a higher mean percentage of spermatozoa exhibiting diffuse H2B staining than did fertile men (7.7% ± 4.6% vs. 1.6% ± 1.2%, respectively, P < 0.01). We observed significant relationships between the proportion of spermatozoa with diffuse nuclear histone staining and both sperm %DFI (r= 0.63, P < 0.01) and sperm %HDS (r= 0.63, P < 0.01). Conclusion: The data demonstrate that infertile men have a higher proportion of spermatozoa with diffuse histone H2B than do fertile men and suggest that sperm DNA damage might, at least in part, be due to abnormally high histone H2B levels.

  10. Itga2b regulation at the onset of definitive hematopoiesis and commitment to differentiation.

    Directory of Open Access Journals (Sweden)

    Stephanie Dumon

    Full Text Available Product of the Itga2b gene, CD41 contributes to hematopoietic stem cell (HSC and megakaryocyte/platelet functions. CD41 expression marks the onset of definitive hematopoiesis in the embryo where it participates in regulating the numbers of multipotential progenitors. Key to platelet aggregation, CD41 expression also characterises their precursor, the megakaryocyte, and is specifically up regulated during megakaryopoiesis. Though phenotypically unique, megakaryocytes and HSC share numerous features, including key transcription factors, which could indicate common sub-regulatory networks. In these respects, Itga2b can serve as a paradigm to study features of both developmental-stage and HSC- versus megakaryocyte-specific regulations. By comparing different cellular contexts, we highlight a mechanism by which internal promoters participate in Itga2b regulation. A developmental process connects epigenetic regulation and promoter switching leading to CD41 expression in HSC. Interestingly, a similar process can be observed at the Mpl locus, which codes for another receptor that defines both HSC and megakaryocyte identities. Our study shows that Itga2b expression is controlled by lineage-specific networks and associates with H4K8ac in megakaryocyte or H3K27me3 in the multipotential hematopoietic cell line HPC7. Correlating with the decrease in H3K27me3 at the Itga2b Iocus, we find that following commitment to megakaryocyte differentiation, the H3K27 demethylase Jmjd3 up-regulation influences both Itga2b and Mpl expression.

  11. Magnetic properties of ball-milled TbFe2 and TbFe2B

    Indian Academy of Sciences (India)

    J Arout Chelvane; S Kasiviswanathan; M V Rao; G Markandeyulu

    2004-04-01

    The magnetic properties of ball-milled TbFe2 and TbFe2B were studied by magnetization measurements. X-ray diffraction studies on TbFe2B showed that boron occupied interstitial position in the crystal structure, just as hydrogen did. The value of the saturation magnetization of TbFe2B was found to be smaller than that of TbFe2. This is explained on the basis of a charge transfer between the boron atoms and the 3d band of Fe. The anisotropy of TbFe2B was found to be large compared to that of TbFe2. X-ray diffractograms for the ball milled samples showed that after 80 h of milling, a predominantly amorphous phase was obtained. TbFe2B was found to undergo easy amorphization compared to TbFe2. Magnetization of TbFe2 was found to decrease rapidly with initial milling hours and was found to be constant with further hours of milling. TbFe2B exhibited an anomalous behaviour with an increase in moment with milling hours and this may be due to the segregation of -Fe.

  12. Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension.

    Science.gov (United States)

    Karmouty-Quintana, Harry; Philip, Kemly; Acero, Luis F; Chen, Ning-Yuan; Weng, Tingting; Molina, Jose G; Luo, Fayong; Davies, Jonathan; Le, Ngoc-Bao; Bunge, Isabelle; Volcik, Kelly A; Le, Thanh-Thuy T; Johnston, Richard A; Xia, Yang; Eltzschig, Holger K; Blackburn, Michael R

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal, fibroproliferative disease. Pulmonary hypertension (PH) can develop secondary to IPF and increase mortality. Alternatively, activated macrophages (AAMs) contribute to the pathogenesis of both IPF and PH. Here we hypothesized that adenosine signaling through the ADORA2B on AAMs impacts the progression of these disorders and that conditional deletion of ADORA2B on myeloid cells would have a beneficial effect in a model of these diseases. Conditional knockout mice lacking ADORA2B on myeloid cells (Adora2B(f/f)-LysM(Cre)) were exposed to the fibrotic agent bleomycin (BLM; 0.035 U/g body weight, i.p.). At 14, 17, 21, 25, or 33 d after exposure, SpO2, bronchoalveolar lavage fluid (BALF), and histologic analyses were performed. On day 33, lung function and cardiovascular analyses were determined. Markers for AAM and mediators of fibrosis and PH were assessed. Adora2B(f/f)-LysM(Cre) mice presented with attenuated fibrosis, improved lung function, and no evidence of PH compared with control mice exposed to BLM. These findings were accompanied by reduced expression of CD206 and arginase-1, markers for AAMs. A 10-fold reduction in IL-6 and a 5-fold decrease in hyaluronan, both linked to lung fibrosis and PH, were also observed. These data suggest that activation of the ADORA2B on macrophages plays an active role in the pathogenesis of lung fibrosis and PH.

  13. Competency-orientated brand cooperations of power supply companies in the B2B sector; Kompetenzorientierte Markenkooperationen von Energieversorgungsunternehmen im B2B-Kundenbereich

    Energy Technology Data Exchange (ETDEWEB)

    Peuser, M.M.

    2008-07-01

    On the basis of an extensive empirical study with B2B electricity users, the author of the book under consideration examines brand co-operations of power supply companies with companies not working in the area of energy production. Based on the view of various co-operation alternatives, impact relations and success-determining factors of influence in the area of B2B customers are identified. The term of the authority of an energy brand is discussed. Beside this, profiles of concrete brands of current power supply companies from the view of B2B customers are pointed out, and recommendations for the organization of brand co-operation and the structure of mark authority in practice are shown. This contribution is written for lecturers and students of the management economics with the emphasis of marketing and management as well as high-level personnel in the energy industry, who wants to develop strong mark authority by brand co-operation.

  14. Heat and charge transport in YNi{sub 2}B{sub 2}C and HoNi{sub 2}B{sub 2}C single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M; Gladun, A; Kreyssig, A [Institut fuer Festkoerperphysik, Technische Universitaet Dresden, D-01062 Dresden (Germany); Wosnitza, J [Hochfeld-Magnetlabor Dresden (HLD), Forschungszentrum Dresden-Rossendorf, D-01314 Dresden (Germany); Petzold, V; Rosner, H [Max-Planck-Institut fuer Chemische Physik fester Stoffe, D-01187 Dresden (Germany); Behr, G; Souptel, D; Mueller, K-H; Drechsler, S-L; Fuchs, G [Leibniz-Institut fuer Festkoerper- und Werkstoffforschung Dresden (IFW), D-01171 Dresden (Germany)], E-mail: M.Schneider@ifw-dresden.de, E-mail: G.Fuchs@ifw-dresden.de

    2008-04-30

    For a systematic investigation of the heat- and charge-transport properties of YNi{sub 2}B{sub 2}C and HoNi{sub 2}B{sub 2}C, single-crystal measurements of the electrical resistivity, the thermal conductivity, and the thermoelectric power were performed on the same samples. For HoNi{sub 2}B{sub 2}C, a local maximum of the Lorenz number at 20 K is evidently connected with the occurrence of magnetic fluctuations well above the ordering temperature. For the in-plane thermal conductivity, a kink near the superconducting transition was observed, consistent with an anisotropic gap or a multiband description. For both investigated borocarbides, the electrical resistance is isotropic. In contrast, the thermal conductivity shows a pronounced anisotropy. The thermoelectric power exhibits a minor anisotropy and can be well described by electron-diffusion and phonon-drag contributions over a wide temperature range. Based on an analysis of full-potential local-orbital calculations, a strong influence of the boron z position on the thermoelectric power has been revealed.

  15. Research on Game Theory of C2B Platform for Recycling%C2B 平台竞价回收博弈研究

    Institute of Scientific and Technical Information of China (English)

    李春发; 刘一非; 王帅

    2016-01-01

    C2B 网络回收平台的竞价回收机制决定了众多回收商之间存在着激烈的竞争,每个网络回收商的回收量不仅取决于自己的回收价格,还取决于其他网络回收商的回收价格。期望利润最大化是每个网络回收商的竞争目标。运用最优化理论与非合作博弈理论证明 C2B 平台竞价回收博弈存在唯一的 Nash 均衡。在完全竞争与串谋合作的不同情况中发现,完全竞争情况下 Nash 均衡的网络回收价格高于串谋合作下的网络回收价格,并通过数值仿真进行验证。%Many recyclers recycle waste products or used fine products and remanufacture for profit in C2B network plat-form.Since the auction collection mechanism of C2B network platform determines there is a fierce competition among the many recyclers,the recycling number of waste products depends on the cost of recycling itself,but also the price of compet-itors.Expected profit maximization is the objective of each network recycler.Firstly the paper studied the operation of the C2B network platform,and proved the bidding games fit the supermodel game by using the theory of optimum and non -co-operative game theory,and the existence of Nash equilibrium.In perfect competition and collusion cooperation cases,we found the recycling price is higher than the conspiracy cooperation network cost under Nash equilibrium,which is verified by using the method of numerical simulation.

  16. An i2b2-based, generalizable, open source, self-scaling chronic disease registry.

    Science.gov (United States)

    Natter, Marc D; Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D

    2013-01-01

    Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.

  17. Serotonin receptors and heart valve disease--it was meant 2B.

    Science.gov (United States)

    Hutcheson, Joshua D; Setola, Vincent; Roth, Bryan L; Merryman, W David

    2011-11-01

    Carcinoid heart disease was one of the first valvular pathologies studied in molecular detail, and early research identified serotonin produced by oncogenic enterochromaffin cells as the likely culprit in causing changes in heart valve tissue. Researchers and physicians in the mid-1960s noted a connection between the use of several ergot-derived medications with structures similar to serotonin and the development of heart valve pathologies similar to those observed in carcinoid patients. The exact serotonergic target that mediated valvular pathogenesis remained a mystery for many years until similar cases were reported in patients using the popular diet drug Fen-Phen in the late 1990s. The Fen-Phen episode sparked renewed interest in serotonin-mediated valve disease, and studies led to the identification of the 5-HT(2B) receptor as the likely molecular target leading to heart valve tissue fibrosis. Subsequent studies have identified numerous other activators of the 5-HT(2B) receptor, and consequently, the use of many of these molecules has been linked to heart valve disease. Herein, we: review the molecular properties of the 5-HT(2B) receptor including factors that differentiate the 5-HT(2B) receptor from other 5-HT receptor subtypes, discuss the studies that led to the identification of the 5-HT(2B) receptor as the mediator of heart valve disease, present current efforts to identify potential valvulopathogens by screening for 5-HT(2B) receptor activity, and speculate on potential therapeutic benefits of 5-HT(2B) receptor targeting. Copyright © 2011. Published by Elsevier Inc.

  18. Thermal behaviour analysis on ITER component cooling water system loop 2B

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Bin, E-mail: guobin@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Fu, Peng [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Dell’Orco, Giovanni; Liliana, Teodoros; Tao, Jun [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Yang, Lei [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2015-11-15

    Highlights: • Thermal hydraulic analysis model has been developed to perform thermal analysis on the component cooling water system loop 2B. • The cooling water temperature profile at client inlet and outlet during one cycle of the most demanding plasma operation scenario was obtained. • Operation behaviour of the main heat exchanger for CCWS-2B has been depicted. - Abstract: ITER cooling water system is composed by several cooling loops, the primary heat transfer loops that form the Tokamak Cooling Water System (TCWS), the secondary heat transfer loops that form the Component Cooling Water System (CCWS) and the Chilled Water System (CHWS) and a tertiary heat transfer loop which is the Heat Rejection System (HRS). The CCWS is further divided into CCWS-1, CCWS-2A, CCWS-2B, CCWS-2C, CCWS-2D depending on the water chemistry needs of clients and wetted area material. The component cooling water system loop 2B (CCWS-2B) has the function to remove heat load from coil power supply component, Neutral Beam Injectors (NBIs) system component and diagnostic system which are located in different buildings. As the total number of the client connections for the loop is a few hundreds, simplified thermal hydraulic analysis model has been developed to perform thermal analysis on the component cooling water system loop 2B. The curve of the cooling water temperature at client inlet and outlet during one cycle of the most demanding plasma operation scenario was obtained and the cooling water flow rate can meet the thermal removal requirement of client was also confirmed from this analysis. In addition, operation behaviour of the main heat exchanger for CCWS-2B in this thermal analysis was depicted for main heat exchanger selection purposes. This study has been carried out with the AFT Fathom code.

  19. LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B

    Science.gov (United States)

    Poirault-Chassac, Sonia; Adam, Frédéric; Muczynski, Vincent; Aymé, Gabriel; Casari, Caterina; Bordet, Jean-Claude; Soukaseum, Christelle; Rothschild, Chantal; Proulle, Valérie; Pietrzyk-Nivau, Audrey; Berrou, Eliane; Christophe, Olivier D.; Rosa, Jean-Philippe; Lenting, Peter J.; Bryckaert, Marijke; Baruch, Dominique

    2016-01-01

    von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations of von Willebrand factor (vWF) that enhance its binding to platelet glycoprotein Ibα and alter the protein’s multimeric structure. Patients with VWD-type 2B display variable extents of bleeding associated with macrothrombocytopenia and sometimes with thrombopathy. Here, we addressed the molecular mechanism underlying the severe macrothrombocytopenia both in a knockin murine model for VWD-type 2B by introducing the p.V1316M mutation in the murine Vwf gene and in a patient bearing this mutation. We provide evidence of a profound defect in megakaryocyte (MK) function since: (a) the extent of proplatelet formation was drastically decreased in 2B MKs, with thick proplatelet extensions and large swellings; and (b) 2B MKs presented actin disorganization that was controlled by upregulation of the RhoA/LIM kinase (LIMK)/cofilin pathway. In vitro and in vivo inhibition of the LIMK/cofilin signaling pathway rescued actin turnover and restored normal proplatelet formation, platelet count, and platelet size. These data indicate, to our knowledge for the first time, that the severe macrothrombocytopenia in VWD-type 2B p.V1316M is due to an MK dysfunction that originates from a constitutive activation of the RhoA/LIMK/cofilin pathway and actin disorganization. This suggests a potentially new function of vWF during platelet formation that involves regulation of actin dynamics. PMID:27734030

  20. Dysregulated Lysine Acetyltransferase 2B Promotes Inflammatory Bowel Disease Pathogenesis Through Transcriptional Repression of Interleukin-10.

    Science.gov (United States)

    Bai, Alfa H C; Wu, William K K; Xu, Liangliang; Wong, Sunny H; Go, Minnie Y; Chan, Anthony W H; Harbord, Marcus; Zhang, Shenghong; Chen, Minhu; Wu, Justin C Y; Chan, Michael W Y; Chan, Matthew T V; Chan, Francis K L; Sung, Joseph J Y; Yu, Jun; Cheng, Alfred S L; Ng, Siew C

    2016-06-01

    Accumulating evidence supports epigenetic modifications in mediating intestinal immunity in inflammatory bowel disease [IBD] pathogenesis. This study aimed to identify key dysregulated epigenetic modulators and the molecular downstream pathways in IBD. Expression of 116 well-defined epigenetic modulators was profiled and validated in 96 intestinal tissues from patients with Crohn's disease [CD], ulcerative colitis [UC], and healthy controls using quantitative reverse transcriptase polymerase chain reaction [QRT-PCR], western blot, and immunohistochemistry. Dysregulation of histone modifications and IBD-related cytokines were examined by chromatin immunoprecipitation, luciferase activity, and gene expression analyses in normal colonic epithelial cell line, NCM460, upon small-molecule inhibition or RNA interference, followed by validation in primary colonic tissues. Targeted expression profiling uncovered seven differentially expressed epigenetic modulators, of which the down-regulation of lysine acetyltransferase 2B [KAT2B] mRNA and protein was the most significant and was consequently validated in inflamed CD and UC compared with healthy colonic tissues. KAT2B protein localised abundantly in nuclei of normal colonic epithelium but diminished in paired inflamed CD and UC tissues. Pharmacological inhibition of KAT2B by anacardic acid in NCM460 cells reduced the levels of histone H4 lysine 5 acetylation [H4K5ac] and interleukin-10 [IL-10] in a dose-dependent manner. Knockdown of KAT2B reduced the IL-10 promoter occupancy of KAT2B and H4K5ac, resulting in transcriptional silencing. IL-10 level was also diminished in inflamed IBD tissues. Our findings demonstrated a novel epigenetic mechanism of IL-10 dysregulation in IBD. Down-regulation of KAT2B may disrupt the innate and adaptive inflammatory responses due to the suppression of this crucial anti-inflammatory cytokine. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University

  1. Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome.

    Science.gov (United States)

    Wilson, Gabrielle R; Sunley, Jasmine; Smith, Katherine R; Pope, Kate; Bromhead, Catherine J; Fitzpatrick, Elizabeth; Di Rocco, Maja; van Steensel, Maurice; Coman, David J; Leventer, Richard J; Delatycki, Martin B; Amor, David J; Bahlo, Melanie; Lockhart, Paul J

    2014-06-01

    Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal recessive disorder characterized by coarse facies, thick skin, acne conglobata, dysmorphic facies, vertebral abnormalities and mitral valve prolapse. We identified a consanguineous kindred with a child clinically diagnosed with BDCS. Linkage analysis of this family (BDCS1) identified five regions homozygous by descent with a maximum LOD score of 1.75. Linkage analysis of the family that originally defined BDCS (BDCS3) identified an overlapping linkage peak at chromosome 5q35.1. Sequence analysis identified two different homozygous mutations in BDCS1 and BDCS3, affecting the gene encoding the protein SH3 and PX domains 2B (SH3PXD2B), which localizes to 5q35.1. Western blot analysis of patient fibroblasts derived from affected individuals in both families demonstrated complete loss of SH3PXD2B. Homozygosity mapping and sequence analysis in a second published BDCS family (BDCS2) excluded SH3PXD2B. SH3PXD2B is required for the formation of functional podosomes, and loss-of-function mutations in SH3PXD2B have recently been shown to underlie 7 of 13 families with Frank-Ter Haar syndrome (FTHS). FTHS and BDCS share some overlapping clinical features; therefore, our results demonstrate that a proportion of BDCS and FTHS cases are allelic. Mutations in other gene(s) functioning in podosome formation and regulation are likely to underlie the SH3PXD2B-mutation-negative BDSC/FTHS patients.

  2. e-Relationships for e-Readiness:culture and corruption in international e-B2B

    OpenAIRE

    Berthon, Pierre; Pitt, Leyland; Berthon, Jean-Paul; Campbell, Colin; Thwaites, Des

    2008-01-01

    The role of electronic networks in B2B relationships has been growing exponentially. From massive internet B2B exchanges to tiny RFID chips, B2B is increasingly becoming e-B2B. Whilst e-B2B has been explored intra-nationally, its international counterpart is less well documented; as has been the role that culture might play in the development of international e-B2B relationships. In this paper we address this important issue of international e-business relationships. Specifically we explore t...

  3. Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region deficient mice

    Science.gov (United States)

    Lee, Eun-Jeong; Peng, Jun; Radke, Michael; Gotthardt, Michael; Granzier, Henk L

    2010-01-01

    Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length. We tested this hypothesis in a mouse model (N2B KO model) in which titin-based passive tension is elevated as a result of the excision of the N2B element, one of cardiac titin’s spring elements. LDA was assessed by measuring the active tension-pCa (−log[Ca2+]) relationship at sarcomere length (SLs) of 1.95, 2.10 and 2.30 µm in WT and N2B KO skinned myocardium. LDA was positively correlated with titin-based passive tension, due to an increase in calcium sensitivity at the longer SLs in the KO. For example, at pCa 6.0 the KO:WT tension ratio was 1.28 ± 0.07 and 1.42 ± 0.04 at SLs of 2.1 and 2.3 µm, respectively. There was no difference in protein expression or phosphorylation of sarcomeric proteins. We also measured the calcium sensitivity after PKA treating the skinned muscle and found that titin-based passive tension was also now correlated with LDA, with a slope that was significantly increased compared to no PKA treatment. Finally, we performed isolated heart experiments and measured the Frank-Starling relation (slope of developed wall stress-LV volume relation) as well as diastolic stiffness (slope of diastolic wall stress – volume relation). The FSM was more pronounced in the N2B KO hearts and the slope of the FSM correlated with diastolic stiffness. These findings support that titin-based passive tension triggers an increase in calcium sensitivity at long sarcomere length, thereby playing an important role in the Frank-Starling mechanism of the heart. PMID:20507834

  4. Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice.

    Science.gov (United States)

    Lee, Eun-Jeong; Peng, Jun; Radke, Michael; Gotthardt, Michael; Granzier, Henk L

    2010-09-01

    Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length. We tested this hypothesis in a mouse model (N2B KO model) in which titin-based passive tension is elevated as a result of the excision of the N2B element, one of cardiac titin's spring elements. LDA was assessed by measuring the active tension-pCa (-log[Ca(2+)]) relationship at sarcomere length (SLs) of 1.95, 2.10, and 2.30 microm in WT and N2B KO skinned myocardium. LDA was positively correlated with titin-based passive tension due to an increase in calcium sensitivity at the longer SLs in the KO. For example, at pCa 6.0, the KO:WT tension ratio was 1.28+/-0.07 and 1.42+/-0.04 at SLs of 2.1 and 2.3 microm, respectively. There was no difference in protein expression or total phosphorylation of sarcomeric proteins. We also measured the calcium sensitivity after PKA treating the skinned muscle and found that titin-based passive tension was also now correlated with LDA, with a slope that was significantly increased compared to no PKA treatment. Finally, we performed isolated heart experiments and measured the Frank-Starling relation (slope of developed wall stress-LV volume relation) as well as diastolic stiffness (slope of diastolic wall stress-volume relation). The FSM was more pronounced in the N2B KO hearts and the slope of the FSM correlated with diastolic stiffness. These findings support that titin-based passive tension triggers an increase in calcium sensitivity at long sarcomere length, thereby playing an important role in the Frank-Starling mechanism of the heart.

  5. Inhibitory Effects of Garcinia cambogia Extract on CYP2B6 Enzyme Activity.

    Science.gov (United States)

    Yu, Jun Sang; Choi, Min Sun; Park, Jong Suk; Rehman, Shaheed Ur; Nakamura, Katsunori; Yoo, Hye Hyun

    2017-03-13

    This study assessed the inhibitory effects of Garcinia cambogia extract on the cytochrome P450 enzymes in vitro. G. cambogia extract was incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes and recombinant CYP2B6 isozyme, and the formation of the marker metabolites was measured to investigate the inhibitory potential on cytochrome P450 enzyme activities. The results showed that G. cambogia extract has significant inhibitory effects on CYP2B6 activity in a concentration-dependent manner. Furthermore, the inhibition was potentiated following preincubation with NADPH, indicating that G. cambogia extract is a time-dependent inhibitor of CYP2B6. Meanwhile, hydroxycitric acid, the major bioactive ingredient of G. cambogia extract, did not exhibit significant inhibition effects on cytochrome P450 enzyme activities. G. cambogia extract could modulate the pharmacokinetics of CYP2B6 substrate drugs and lead to interactions with those drugs. Therefore, caution may be required with respect to concomitant intake of dietary supplements containing G. cambogia extract with CYP2B6 substrates.

  6. Involvement of CYP2B6 in the biotransformation of propofol by human liver microsomes

    Institute of Scientific and Technical Information of China (English)

    TANG Bing; WANG Jun-ke; FENG Wan-yu

    2008-01-01

    Objective To determine whether the cytochrome P4502B6 (CYP2B6) is involved in the oxidation of propofol by human liver microsomes. Methods The change of propofol concentration in an incubation mixture with human liver microsomes was monitored by the high performance liquid chromatography (HPLC), in order to calculate the rate constants of metabolism of propofol. The correlation between the rate constants and the rate of metabolism of CYP2B6 selective substrate bupropion, and the effect of two different CYP2B6 specific inhibitors on the propofol metabolism were examined. Results The mean rate constant of propofol metabolism by liver microsomes obtained from twelve individuals was 3.9 (95 % confidence intervals 3.3, 4.5) nmol·min-1·mg-1 protein. The rate constants of propofol metabolism by liver microsomes were significantly correlated with bupropion hydroxylation (r=0.888, P<0.001). Both selective chemical inhibitors of CYP2B6, orphenadrine and N, N′, N″-triethylenethiophosphoramide (thioTEPA), reduced the rate constants of propofol metabolism by 37.596 (P<0.001) and 42.796 (P<0.001)in liver microsomes, respectively. Conclusions CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes.

  7. Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.

    Science.gov (United States)

    Aguilera-Pesantes, Daniel; Méndez, Miguel A

    2017-02-08

    While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.

  8. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    Directory of Open Access Journals (Sweden)

    Wiebke Janssen

    2015-01-01

    Full Text Available Objective. The serotonin (5-HT pathway was shown to play a role in pulmonary hypertension (PH, but its functions in right ventricular failure (RVF remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist or SB204741 (5-HT2B receptor antagonist on right heart function and structure upon pulmonary artery banding (PAB in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid or SB204741 (5 mg/kg day. Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI, and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF.

  9. 5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure.

    Science.gov (United States)

    Janssen, Wiebke; Schymura, Yves; Novoyatleva, Tatyana; Kojonazarov, Baktybek; Boehm, Mario; Wietelmann, Astrid; Luitel, Himal; Murmann, Kirsten; Krompiec, Damian Richard; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Weissmann, Norbert; Seeger, Werner; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo

    2015-01-01

    The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions in right ventricular failure (RVF) remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B receptor antagonist) on right heart function and structure upon pulmonary artery banding (PAB) in mice. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid) or SB204741 (5 mg/kg day). Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF.

  10. Supporting the Health Quality Measures Format in i2b2.

    Science.gov (United States)

    Klann, Jeffrey G; Murphy, Shawn N

    2013-01-01

    The Health Quality Measures Format (HQMF) is an HL7 standard for expressing computable queries of clinical data. It is becoming increasingly consequential for both quality measurement and population health research. A variety of national leadership is involved in its development and deployment, including the Meaningful Use incentive program, the Query Health initiative, the Joint Commission, the National Quality Forum (NQF), and the Food and Drug Administration. Here we analyze the structure of HQMF and apply this to computation of HQMF on Informatics for Integrating Biology and the Bedside (i2b2). i2b2 is a widely used, modular, open-source clinical research data repository. We implement a translator to convert between HQMF and i2b2-XML format that covers the subset of HQMF supported in i2b2-XML, which will be expanded in the next release of i2b2. This translator is part of the freely-available reference implementation of the QueryHealth initiative.

  11. Molecular level interaction of inositol hexaphosphate with the C2B domain of human synaptotagmin I.

    Science.gov (United States)

    Joung, Meng-Je; Mohan, Sepuru K; Yu, Chin

    2012-05-01

    Synaptotagmin I is a synaptic vesicle membrane protein that serves as a multifunctional regulator during the exocytosis of neurotransmitter release. It contains C2A and C2B domains. The binding of Ca(2+) to the C2A domain activates the exocytosis of secretory vesicles, while the binding of inositol polyphosphates (IP4-IP6) to the C2B domain inhibits this process. To understand the IP6-induced inhibition of exocytosis of secretory vesicles, we determined the three-dimensional structure of the C2B-IP6 complex by nuclear magnetic resonance (NMR). In this study, we have determined the binding constant by isothermal titration calorimetry. The circular dichroism measurements demonstrated that IP6 can stabilize the C2B molecule. We identified the binding site using (1)H-(15)N heteronuclear single-quantum coherence spectroscopy titration data and determined the structure of the C2B-IP6 complex using multidimensional NMR studies. This information will aid in the design of better pharmacological treatments for neurological disorders.

  12. Serotonin 2B receptor: upregulated with age and hearing loss in mouse auditory system.

    Science.gov (United States)

    Tadros, Sherif F; D'Souza, Mary; Zettel, Martha L; Zhu, XiaoXia; Lynch-Erhardt, Martha; Frisina, Robert D

    2007-07-01

    Serotonin (5-HT) is a monoamine neurotransmitter. Serotonin may modulate afferent fiber discharges in the cochlea, inferior colliculus (IC) and auditory cortex. Specific functions of serotonin are exerted upon its interaction with specific receptors; one of those receptors is the serotonin 2B receptor. The aim of this study was to investigate the differences in gene expression of serotonin 2B receptors with age in cochlea and IC, and the possible correlation between gene expression and functional hearing measurements in CBA/CaJ mice. Immunohistochemical examinations of protein expression of IC in mice of different age groups were also performed. Gene expression results showed that serotonin 2B receptor gene was upregulated with age in both cochlea and IC. A significant correlation between gene expression and functional hearing results was established. Immunohistochemical protein expression studies of IC showed more serotonin 2B receptor cells in old mice relative to young adult mice, particularly in the external nucleus. We conclude that serotonin 2B receptors may play a role in the pathogenesis of age-related hearing loss.

  13. Modified Anion Packing of Na2B12H12 in Close to Room Temperature Superionic Conductors.

    Science.gov (United States)

    Sadikin, Yolanda; Schouwink, Pascal; Brighi, Matteo; Łodziana, Zbigniew; Černý, Radovan

    2017-05-01

    Three different types of anion packing, i.e., hexagonal close packed (hcp), cubic close packed (ccp), and body centered cubic (bcc), are investigated experimentally and with ab initio calculations in the model system Na2B12H12. Solvent free and water assisted mechanical grinding provide polycrystalline samples for temperature-dependent synchrotron radiation X-ray powder diffraction and electrochemical impedance spectroscopy. It is shown that among the common close packed lattices, the hcp anionic backbone creates very favorable conditions for three-dimensional ionic conduction pathways, comprised of O-O, T-T, and T-O-T (O for octahedral, T for tetrahedral) cation hops. The hcp lattice is stable with respect to ccp and bcc lattices only at higher volumes per formula unit, which is achieved either by cationic substitution with larger cations or partial substitution of hydrogen by iodine on the closo-anion. It is found that the partial cationic substitution of sodium with lithium, potassium, or cesium does not lead to enhanced conductivity due to the obstruction of the conduction pathway by the larger cation located on the octahedral site. Substitution on the closo-anion itself shows remarkable positive effects, the ionic conductivity of Na2B12H12-xIx reaching values of close to 10(-1) S cm(-1) at a rather low temperature of 360 K. While the absolute value of σ is comparable to that of NaCB11H12, the temperature at which it is attained is approximately 20 K lower. The activation energy of 140 meV is determined from the Arrhenius relation and among the lowest ever reported for a Na-conducting solid.

  14. 77 FR 24225 - Information Collection Approval; Temporary Non-Agricultural Employment of H-2B Aliens in the...

    Science.gov (United States)

    2012-04-23

    ... of H-2B Aliens in the United States AGENCY: Employment and Training Administration, Department of... Employment of H-2B Aliens in the United States; Final Rule. See 77 FR 10038, Feb. 21, 2012. DATES: On April 8...

  15. Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C

    DEFF Research Database (Denmark)

    Hauser, Goran; Awad, Tahany; Thorlund, Kristian

    2014-01-01

    BACKGROUND: A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin still represents standard treatment of chronic hepatitis C infection in the majority of patients. However, it is not established which of the two licensed peginterferon products, peginterferon alpha-2......a or peginterferon alpha-2b, is the most effective and has a better safety profile. OBJECTIVES: To systematically evaluate the benefits and harms of peginterferon alpha-2a versus peginterferon alpha-2b in head-to-head randomised clinical trials in patients with chronic hepatitis C. SEARCH METHODS...... literature. SELECTION CRITERIA: We included randomised clinical trials comparing peginterferon alpha-2a versus peginterferon alpha-2b given with or without co-intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi-randomised studies and observational studies as identified by the searches...

  16. Uso de una conantokina y anticuerpos policlonales para identificar la subunidad NR2B del receptor

    OpenAIRE

    2010-01-01

    Objetivo. Proponer una metodología de identificación de la subunidad NR2B, mediante el uso de conantokina G, así como una adecuada extracción de la subunidad NR2B. Materiales y métodos. Se ensayaron dos metodologías para la extracción de la subunidad NR2B de cerebro de rata adulta, la primera buscó la extracción de la subunidad a partir de la membrana mediante la utilización del detergente deoxicolato de sodio y la segunda, garantizó primero la solubilización y eliminación de proteínas citopl...

  17. The Importance of Brand on B2B Markets: Expert Interviews with Hilti AG Managers

    Directory of Open Access Journals (Sweden)

    Martin Konečný

    2013-12-01

    Full Text Available This paper investigates the importance of brand building in the business-to-business world. Not only B2C companies must take branding into account and put it among their top priorities in order to survive and succeed on the market. The first part of the article deals with the theoretical background of brand importance and market specifics of B2B markets and results in the setting of two hypotheses. The following research has to find out how the managers of a pure business-to-business company perceive the importance of a brand; moreover, it has to evaluate the importance of eight specific brand building factors. Fourteen expert interviews document the growing of brands in the B2B market and their main aspects. At the end of the article, we will focus on future implications for B2B management.

  18. Magnetic properties of Y1- xGdxCo2B2C series of borocarbides

    Science.gov (United States)

    Bud'ko, S. L.; Giordanengo, B.; Sulpice, A.; Fontes, M. B.; Baggio-Saitovitch, E. M.

    1995-04-01

    Magnetic properties of Y1- xGdxCo2B2C series of compounds were studied. Two magnetically ordered phases were observed for 0.7 ≤ x ≤ 1. Change of the magnetic ordering temperatures T 1 and T 2 with the Gd concentration is argued to be related to the dilution of magnetic Gd by nonmagnetic Y and to the reduction of the distance between ( Y1- xGdx) C planes. However, significant contribution to the changes in T 1 between pure GdNi2B2C and GdCo2B2C samples is suggested to be due to the different 3 d band filling in these compounds.

  19. A new natural naphtho[1,2-b]furan from the leaves of Cassia fistula.

    Science.gov (United States)

    Wang, Li-Qin; Tang, Zheng-Rong; Mu, Wei-Hua; Kou, Jun-Feng; He, Dong-Yang

    2013-11-01

    A new naphtho[1,2-b]furan, 2,9-dihydroxy-7-methoxy-4-methylnaphtha[1,2-b]furan-3(2H)-one (1), along with 10 known compounds vanillic acid (2), naringenin (3), glyceryl-1-tetracosanoate (4), moracin J (5), 1,3,8-trihydroxyanthraquinone (6), esculetin (7), mauritianin (8), kaempferol 3-neohesperidoside (9), β-sitosterol (10), and β-daucosterol (11), was isolated from the leaves of Cassia fistula. The structure of the new compound was determined by NMR and X-ray analysis. Compounds 1, 3, 5-9 were isolated from this plant for the first time. The naphtha[1,2-b]furan was firstly isolated from the natural resources.

  20. Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.

    Directory of Open Access Journals (Sweden)

    Raquel María Fernández

    Full Text Available Hirschsprung disease (HSCR is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neural crest derivatives, and heterozygous mutations cause a complex dysautonomia associating HSCR, Congenital Central Hypoventilation Syndrome (CCHS and neuroblastoma (NB in various combinations. In order to determine the role of PHOX2B in isolated HSCR, we performed a mutational screening in a cohort of 207 Spanish HSCR patients. Our most relevant finding has been the identification of a de novo and novel deletion (c.393_410del18 in a patient with HSCR. Results of in silico and functional assays support its pathogenic effect related to HSCR. Therefore our results support that PHOX2B loss-of-function is a rare cause of HSCR phenotype.

  1. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  2. Laboratory Study of O2(b1Σ g+, υ = 1) Collisional Removal at Thermospheric Temperatures

    Science.gov (United States)

    Wouters, E. R.; Pejaković, D. A.; Phillips, K. E.; Kalogerakis, K. S.

    2003-12-01

    In the Earth's thermosphere, energy transfer from O(1D) to O2 generates oxygen molecules in the υ = 0 and 1 levels of the O2(b1Σg+) state. The emissions in the O2(b1Σ g+ - X3Σ g-) system (Atmospheric Band) present a major component of the Earth's airglow. Interpretation of the measured intensities of O2 Atmospheric Band emissions can yield altitude profiles of oxygen atom density and local temperature in the lower thermosphere. To achieve this goal accurate laboratory measurements of the collisional removal rate coefficients of O2(b, υ = 1) and their temperature dependence are essential. Atmospheric observations suggest that the relevant colliders for the removal of O2(b, υ = 1) in the lower thermosphere are O2 and O(3P). We report measurements of the rate coefficients for the collisional removal of O2(b, υ = 1) by O2, N2, and CO2, at temperatures in the range 300--1000 K. A state-specific two-laser technique is used, in which the visible output of the first laser directly excites O2 to O2(b, υ = 1), and the ultraviolet output of the second laser probes the O2(b, υ = 1) population by resonantly enhanced multiphoton ionization via the υ= 4 level of the d1Π g Rydberg state. The temporal evolution of the O2(b, υ = 1) population is monitored by varying the time delay between the two laser pulses. The rate coefficient of the collisional removal of O2(b, υ = 1) by O2 increases monotonically with temperature from about 1.5 x 10-11 cm3 s-1 to about 6*E-11 cm3 s-1 in the range 300--1000 K. Experiments with colliders N2 and CO2 determine the upper limits for the removal rate coefficients of O2(b, υ = 1) by N2 and CO2 to be 2 orders of magnitude smaller. This work extends previous studies of O2(b, υ = 1) at room and low temperatures.1,2 We are currently planning experiments to investigate the collisional removal of O2(b, υ = 1) by O atoms. This study was supported by the NSF's Grant ATM-0209229. The participation of K. Phillips in this project was funded by

  3. Possible coexistence of superconductivity and magnetic order in NdPt2B2C

    Indian Academy of Sciences (India)

    S K Dhar; A D Chinchure; E Alleno; C Godart; L C Gupta; R Nagarajan

    2002-05-01

    Coexistence of superconductivity and magnetic order has been one of the exciting aspects of the quaternary borocarbide superconductors. So far, RNi2B2C (R=Tm, Er, Ho and Dy) are the only known magnetic superconductors in this family. Here, we present our resistivity, magnetization and heat capacity studies on NdPt2B2C (nominal composition, NdPt1.5Au0.6B2C and NdPt2.1B2.4C1.2). We find superconductivity in both samples with c,onset∼ 3 K. Bulk magnetic order is found to occur below 1.7 K. We suggest that NdPt2B2C is a possible magnetic superconductor.

  4. Reciprocal interactions of Fgf10/Fgfr2b modulate the mouse tongue epithelial differentiation.

    Science.gov (United States)

    Sohn, Wern-Joo; Jung, Hye-In; Choi, Min-A; Han, Jin-Hyun; Gwon, Gi-Jeong; Yamamoto, Hitoshi; Lee, Sanggyu; Ryoo, Zae Young; Park, Eui-Kyun; Shin, Hong-In; Jung, Han-Sung; Kim, Jae-Young

    2011-08-01

    The molecular mechanisms for epithelial differentiation have been studied by observing skin development in embryogenesis, but the early signaling modulations involved in tongue epithelial differentiation are not completely understood. Based on the gene expression patterns of the Fgf signaling molecules and previous results from Fgf10 and Fgfr2b knockout mice, it was hypothesized that there would be fundamental signaling interactions through the epithelial Fgfr2b and its mesenchymal ligand Fgf10 to regulate tongue epithelium differentiation. To elucidate these reciprocal interactions in tongue epithelial differentiation, this study employed an in vitro tongue organ culture system with antisense-oligodeoxynucleotides (AS-ODNs) and recombinant protein-soaked bead implantation for the loss-of-function and gain-of-function studies. Functional analysis of Fgf signaling revealed precise reciprocal interactions, which showed that mesenchymal Fgf10 rather than Fgf7 modulates tongue epithelial differentiation via Fgfr2b in a temporal- and spatial-specific manner.

  5. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia...... chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  6. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  7. Properties of a New Nonlinear Optical Crystal CdZn2B2O6

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fan; SHEN De-Zhong; SHEN Guang-Qiu; WANG Xiao-Qing

    2008-01-01

    @@ Cadmium dizinc diborate (CdZn2B2O6) single crystals have been grown for the first time. The crystal structure of CdZn2B2O6 is the same as that of the Cd3Zn3B4O12. The x-ray diffraction, infrated and Raman spectra,differential scanning calorimetry analysis and density indicate that the physical and chemical properties of both crystals are very similar. Especially, the nonlinear optical coefficients of CdZn2B2O6 and Cd3ZnaB4O12 crystals are 2.6 and 2.4 times as large as that of KH2PO4 crystal respectively. Chemical etching experiments indicated that these crystals are very stable in neutral solution and not hygroscopic in air at room temperature.

  8. Standards-Based Procedural Phenotyping: The Arden Syntax on i2b2.

    Science.gov (United States)

    Mate, Sebastian; Castellanos, Ixchel; Ganslandt, Thomas; Prokosch, Hans-Ulrich; Kraus, Stefan

    2017-01-01

    Phenotyping, or the identification of patient cohorts, is a recurring challenge in medical informatics. While there are open source tools such as i2b2 that address this problem by providing user-friendly querying interfaces, these platforms lack semantic expressiveness to model complex phenotyping algorithms. The Arden Syntax provides procedural programming language construct, designed specifically for medical decision support and knowledge transfer. In this work, we investigate how language constructs of the Arden Syntax can be used for generic phenotyping. We implemented a prototypical tool to integrate i2b2 with an open source Arden execution environment. To demonstrate the applicability of our approach, we used the tool together with an Arden-based phenotyping algorithm to derive statistics about ICU-acquired hypernatremia. Finally, we discuss how the combination of i2b2's user-friendly cohort pre-selection and Arden's procedural expressiveness could benefit phenotyping.

  9. Genes for resistance to stripe rust on chromosome 2B and their application in wheat breeding

    Institute of Scientific and Technical Information of China (English)

    Peigao Luo; Xueyun Hu; Huaiyu Zhang; Zhenglong Ren

    2009-01-01

    Stripe rust,caused by Puccinia striiformis f.sp.tritici,is one of the most damaging diseases of wheat worldwide.Growing resistant cultivars is the most economic and environmental friendly way to control the disease.There are many resistance genes to stripe rust located on wheat chromosome 2B.Here,we propose a strategy to construct the recombinant wheat chromosome 2B with multiple resistances to stripe rust by making crosses between wheat lines or cultivars carrying Yr genes and using marker-assisted selection,based on the reported information about resistance spectrum,chromosomal location,and linked markers of the genes.Pyramiding the resistance genes on 2B would afford a valuable strategy to control the disease by cultivating varieties with durable resistance.The possibility,efficiency,and prospect of the suggested strategy are reviewed in the paper.

  10. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population.

    Directory of Open Access Journals (Sweden)

    Yongfeng Yang

    Full Text Available Schizophrenia (SZ is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case-control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively. Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035, as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10(-8, respectively. After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10(-7. In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849-rs12319804-rs10845851, CC (rs12582848-rs7952915, and AAGAC (rs2041986-rs11055665-rs7314376-rs7297101-rs2098469, had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively. In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively. In conclusion, our study provides novel evidence for an association between GRIN2B

  11. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

    Science.gov (United States)

    Zhang, Hongxing; Yang, Ge; Wang, Xiujuan; Ding, Minli; Jiang, Tianzi; Lv, Luxian

    2015-01-01

    Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between

  12. Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

    Science.gov (United States)

    Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

    2015-01-01

    ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

  13. UBE2B mRNA alterations are associated with severe oligozoospermia in infertile men

    Science.gov (United States)

    Yatsenko, Alexander N.; Georgiadis, Andrew P.; Murthy, Lata J.; Lamb, Dolores J.; Matzuk, Martin M.

    2013-01-01

    Oligozoospermia (low sperm count) is a common semen deficiency. However, to date, few genetic defects have been identified to cause this condition. Moreover, even fewer molecular genetic diagnostic tests are available for patients with oligozoospermia in the andrology clinic. Based on animal and gene expression studies of oligozoospermia, several molecular pathways may be disrupted in post-meiotic spermatozoa. One of the disrupted pathways is protein ubiquitination and cell apoptosis. A critical protein involved in this pathway is the ubiquitin-conjugating enzyme 2B, UBE2B. Absence of Ube2b in male mice causes spermatogenic meiotic disruption with increased apoptosis, leading to infertility. To examine the association between messenger RNA defects in UBE2B and severe oligozoospermia (0.1–10 × 106 cells/ml), sequencing of sperm cDNA in 326 oligozoospermic patients and 421 normozoospermic men was performed. mRNA alterations in UBE2B were identified in sperm in 4.6% (15 out of 326) of the oligozoospermic patients, but not found in control men, suggesting strong association between mRNA defects and oligozoospermia (χ2 = 19, P = 0.0001). Identified UBE2B alterations include nine splicing, four missense and two nonsense alterations. The follow-up screen of corresponding DNA regions did not reveal causative DNA mutations, suggesting a post-transcriptional nature of identified defects. None of these variants were reported in the dbSNP database, although other splicing abnormalities with low level of expression were present in 11 out of 421 (2.6%) controls. Our findings suggest that two distinct molecular mechanisms, mRNA editing and splicing processing, are disrupted in oligozoospermia. We speculate that the contribution of post-transcriptional mRNA defects to oligozoospermia could be greater than previously anticipated. PMID:23378580

  14. Common PHOX2B poly-alanine contractions impair RET gene transcription, predisposing to Hirschsprung disease.

    Science.gov (United States)

    Di Zanni, Eleonora; Adamo, Annalisa; Belligni, Elga; Lerone, Margherita; Martucciello, Giuseppe; Mattioli, Girolamo; Pini Prato, Alessio; Ravazzolo, Roberto; Silengo, Margherita; Bachetti, Tiziana; Ceccherini, Isabella

    2017-07-01

    HSCR is a congenital disorder of the enteric nervous system, characterized by the absence of neurons along a variable length of the gut resulting from loss-of-function RET mutations. Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by impaired response to hypercapnia and hypoxemia caused by heterozygous mutations of the PHOX2B gene, mostly polyalanine (polyA) expansions but also missense, nonsense, and frameshift mutations, while polyA contractions are common in the population and believed neutral. HSCR associated CCHS can present in patients carrying PHOX2B mutations. Indeed, RET expression is orchestrated by different transcriptional factors among which PHOX2B, thus suggesting its possible role in HSCR pathogenesis. Following the observation of HSCR patients carrying in frame trinucleotide deletions within the polyalanine stretch in exon 3 (polyA contractions), we have verified the hypothesis that these PHOX2B variants do reduce its transcriptional activity, likely resulting in a down-regulation of RET expression and, consequently, favouring the development of the HSCR phenotype. Using proper reporter constructs, we show here that the in vitro transactivation of the RET promoter by different HSCR-associated PHOX2B polyA variants has resulted significantly lower compared to the effect of PHOX2B wild type protein. In particular, polyA contractions do induce a reduced transactivation of the RET promoter, milder compared to the severe polyA expansions associated with CCHS+HSCR, and correlated with the length of the deleted trait, with a more pronounced effect when contractions are larger. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Refined Sellmeier and thermo-optic dispersion formulas for Li2B4O7

    Science.gov (United States)

    Umemura, Nobuhiro; Watanabe, Jun; Matsuda, Daisuke; Kamimura, Tomosumi

    2017-03-01

    We report the high-accuracy Sellmeier and thermo-optic dispersion formulas for Li2B4O7, which provide an excellent reproduction of the temperature-dependent phase-matching conditions for second-harmonic generation (SHG) and sum-frequency generation (SFG) in the 0.2093–1.5352 µm range. In addition, Li2B4O7 was found to be nearly 90° phase-matchable for fifth-harmonic generation (5HG) of an Yb-doped fiber laser at 1.031 µm.

  16. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    OpenAIRE

    Wiebke Janssen; Yves Schymura; Tatyana Novoyatleva; Baktybek Kojonazarov; Mario Boehm; Astrid Wietelmann; Himal Luitel; Kirsten Murmann; Damian Richard Krompiec; Aleksandra Tretyn; Soni Savai Pullamsetti; Norbert Weissmann; Werner Seeger; Hossein Ardeschir Ghofrani; Ralph Theo Schermuly

    2015-01-01

    Objective. The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions in right ventricular failure (RVF) remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B receptor antagonist) on right heart function and structure upon pulmonary artery banding (PAB) in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg b...

  17. The Importance of Brand on B2B Markets: Case Study of Hilti

    OpenAIRE

    Konečný, Martin

    2012-01-01

    The brand is mostly associated with business-to-customer markets and environment. People would first think of such a brand, because we see marketing and advertising of those brands every day. But business-to-business brands are for companies also very important. The overall goal of my thesis would be to find out how the managers of a pure B2B company perceive the importance of brand in the B2B environment where the company operates. Theoretical part will, in the first chapter, characterize B2...

  18. The role of transcriptional coactivator ADA2b in Arabidopsis abiotic stress responses.

    Science.gov (United States)

    Vlachonasios, Konstantinos E; Kaldis, Athanasios; Nikoloudi, Adriana; Tsementzi, Despoina

    2011-10-01

    Plant growth and crop production can be greatly affected by common environmental stresses such as drought, high salinity and low temperatures. Gene expression is affected by several abiotic stresses. Stress-inducible genes are regulated by transcription factors and epigenetic mechanisms such as histone modifications. In this Mini-Review, we have explored the role of transcriptional adaptor ADA2b in Arabidopsis responses to abiotic stress. ADA2b is required for the expression of genes involved in abiotic stress either by controlling H3 and H4 acetylation in the case of salt stress or affecting nucleosome occupancy in low temperatures response.

  19. Examination of dioxin degradation conditions for geobacillus midousuji SH2B-J2

    Energy Technology Data Exchange (ETDEWEB)

    Hoshina, S. [Jikei Univ., School of Medicine, Tokyo (Japan); Ohtsuka, Y. [Forestry and Forest Products Research Instiute; Goda, H. [Towa Kagaku Co., Ltd.

    2004-09-15

    Cellular membrane degradation capability of SH2B-J2 strains for dioxin mixtures that are greater than tetra-chlorinated have been examined. Optimal temperature, reaction time, optimal pH, and heavy metal resistance of cellular membrane enzyme were investigated, to examine dioxin degradation characteristics of SH2B-J2 strains. For chlorinated dioxins, a mixture (PCDD/PCDF mix) containing 7 species of dibenzo-p-dioxins greater than tetra-chlorinated, as well as 10 isomers of dibenzofurans, was used. Using GC/MS, decrease of 17 species of dioxin isomer/congener was measured.

  20. An Inter-enterprise Workflow Model for Supply Chain and B2B E-commerce

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The goals of B2B electronic commerce and supply chain management system are to implement interoperability of independent enterprises, to smooth the information flow between them and to deploy business processes over multiple enterprises. The inherent characteristics of workflow system make it suitable to implement the cross organization management. This paper, firstly, proposes an inter-enterprises workflow model based on the agreement to support the construction of supply chain management system and B2B electronic commerce. This model has extended the standard workflow model. After that, an architecture which supports the model has been introduced, especially it details the structure and implementation of interfaces between enterprises.

  1. Short syntheses of enantiopure calystegine B-2, B-3, and B-4

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Madsen, Robert

    2001-01-01

    Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps.......Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps....

  2. How to successfully present a solution in a B2B sales meeting

    OpenAIRE

    Klemola, Mari

    2013-01-01

    This thesis contains research on presenting a solution in a B2B (business-to-business) sales meeting. This thesis is planned to complement the existing course material in the solution selling course at HAAGA-HELIA University of Applied Sciences’ Degree Programme in Sales. The objective of this thesis was to create a handbook to students about how to successfully present a solution in a B2B sales meeting. This is the main research question. The secondary research questions are: (1) how to ...

  3. H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation

    OpenAIRE

    Xu, Zhiliang; Song,Zhenhua; Li, Guoping; Tu, Huayu; Liu, Weixiao; Liu, Yujiao; Wang, Pan; Wang, Yuanting; Cui, Xiuhong; Liu, Chao; Shang, Yongliang; de Rooij, Dirk G.; Gao, Fei; Li, Wei

    2016-01-01

    Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20−/− spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB...

  4. Competence Neworks: Effects on Corporate Branding in B2B SMEs

    OpenAIRE

    2015-01-01

    The purpose of this thesis is to investigate the effects of competence networks on corporate branding in B2B SMEs and to develop a conceptual model of these effects. After reviewing the relevant literature that explores the field, eight components of corporate branding in an effective growth stage of an SME have been identified. Founders Alliance is a competence network in Sweden that was chosen as a case for our study. Representatives of five B2B SMEs within Founders Alliance were interviewe...

  5. Progressive dysphagia in limb-girdle muscular dystrophy type 2B.

    LENUS (Irish Health Repository)

    Walsh, Richard

    2012-02-01

    Dysphagia has not been reported in genetically confirmed limb-girdle muscular dystrophy type 2B (LGMD2B). A 40-year-old woman reported exercise-induced calf pain at age 34, followed by progressive lower and upper limb weakness. At age 38, progressive dysphagia for solids, and subsequently liquids, ensued. Endoscopic and videofluoroscopic-radiological findings indicated a myopathic swallowing disorder. Molecular genetic analysis confirmed two dysferlin gene mutations consistent with a compound heterozygote state. Progressive dysphagia should be considered as part of the expanding dysferlinopathy phenotype.

  6. TiO2(B) nanoparticle-functionalized WO3 nanorods with enhanced gas sensing properties.

    Science.gov (United States)

    Zhang, Hongxin; Wang, Shurong; Wang, Yanshuang; Yang, Jiedi; Gao, Xueling; Wang, Liwei

    2014-06-14

    In this work, TiO2(B) nanoparticle (NP)-functionalized WO3 nanorods (NRs) were synthesized by a two-step solution strategy, with a hydrothermal process for WO3 NRs and hydrolyzation of Ti(OBu)4 for the functionalization of TiO2(B) NPs. Various techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), were employed to investigate the morphology, microstructure, crystalline nature and chemical composition of the prepared TiO2(B) NP-functionalized WO3 NRs. SEM and TEM results revealed that the TiO2(B)-WO3 composite showed a rod-like nanostructure with a diameter in the range from 93 to 154 nm and a rough surface, which could increase the accessible surface area and the amount of surface active sites, thus improving the properties or performance of the as-prepared composite NRs. XRD and XPS analysis clearly verified that monoclinic TiO2(B) NPs, a metastable polymorph of TiO2, were successfully supported on the WO3 NRs. Gas sensing measurement results for several common reductive organic gases such as acetone, ethanol, ether, methanol and formaldehyde demonstrated that the sensor based on the as-obtained TiO2(B) NP-functionalized WO3 NRs exhibited obviously enhanced responses compared with a pure WO3 NR based sensor, as well as fast response-recovery speeds, good reproducibility and good stability, indicating their promising application in gas sensors. The excellent gas sensing performance could be attributed to the unique 1D rod-like nanostructure with a rough surface, the existence of TiO2-WO3 heterojunctions and the catalytic effect of the TiO2(B) NPs. The as-prepared TiO2(B) NP-functionalized WO3 NRs will also have very good prospects in electrochromic devices and catalysis applications.

  7. Jusbetonin, the first indolo[3,2-b]quinoline alkaloid glycoside, from Justicia betonica.

    Science.gov (United States)

    Subbaraju, Gottumukkala V; Kavitha, Jakka; Rajasekhar, Dodda; Jimenez, Jorge I

    2004-03-01

    A new indolo[3,2-b]quinoline alkaloid glycoside, jusbetonin (1), and three known alkaloids, namely, 10H-quindoline (2), 6H-quinindoline (3), and 5H,6H-quinindolin-11-one (4), have been isolated from the leaves of Justicia betonica. The structure of 1 was established on the basis of 1D and 2D NMR ((1)H-(1)H COSY, HMQC, and HMBC) and HRFABMS data. Compound 1 is the first example of a glycosylated indolo[3,2-b]quinoline alkaloid, while compound 4 was isolated for the first time from a natural source.

  8. A New Evolution Mechanism Model for B2B E-Commerce Network

    OpenAIRE

    Zhihong Tian; Zhenji Zhang; Xiaolan Guan

    2013-01-01

    To study the structure and evolution mechanism of B2B e-commerce network, the authors propose a network with several layers description of B2B e-commerce market. The empirical analysis from Alibaba.com shows that degree distribution of the network structure follows power-law. Based on modified BA (Barabasi-Albert) model, a new model is proposed, adding layers, fitness parameters, and more reasonable growth mechanism. The model reveals that, the structure of the network is stable, and the aver...

  9. Anisotropic Multiband Many-Body Interactions in LuNi2B2C

    Energy Technology Data Exchange (ETDEWEB)

    Bergk, B.; Petzold, V.; Rosner, H.; Drechsler, S.-L.; Bartkowiak, M.; Ignatchik, O.; Bianchi, A. D.; Sheikin, I.; Canfield, P. C.; Wosnitza, J.

    2008-06-27

    We present a comprehensive de Haas-van Alphen study on the nonmagnetic borocarbide superconductor LuNi{sub 2}B{sub 2}C. The analysis of the angular-dependent effective masses for different bands in combination with full-potential density functional calculations allowed us to determine the mass-enhancement factors, {lambda}, for the different electronic bands and their wave-vector dependences. Our data clearly show the anisotropic multiband character of the superconductivity in LuNi{sub 2}B{sub 2}C.

  10. Efficient 266 nm Ultraviolet Beam Generation in K2Al2B2O7 Crystal

    Institute of Scientific and Technical Information of China (English)

    吕军华; 王桂玲; 许祖彦; 陈创天; 王继扬; 张承乾; 刘耀岗

    2002-01-01

    The ultraviolet beam at 266 nm was obtained by fourth harmonic generation of 1064 nm Nd:YAG laser radiation through a nonlinear crystal K2Al2 B2O7 (KABO). The fundamental frequency of a Hash-lamp pumped Nd: YAG laser was doubled in a β-Ba2B2O4 crystal to generate a second harmonic output at the wavelength of 532 nm,and then doubled again in the KABO crystal to generate the fourth harmonic output at 266 nm. The optical conversion efficiency from 532 to 266 nm was investigated for the first time, and 13% was achieved.

  11. Density of Na2O-Li2O-SiO2-B2O3 Molten Slag at 1 803-1 873 K

    Institute of Scientific and Technical Information of China (English)

    XIAO Feng; FANG Liang

    2004-01-01

    The density of three kinds of molten slags was measured by modified sessile drop method at 1 803-1 873 K. The density of molten slag is found to decrease with increasing temperature. The temperature coefficients of Na2O-Li2O-SiO2 and Li2O-SiO2-B2O3 slag are smaller than that of Na2O-B2O3 slag. The molar volume of slags increases with increasing temperature.

  12. Molecular and functional characterization of the first tick CAP2b (periviscerokinin) receptor from Rhipicephalus (Boophilus) microplus

    Science.gov (United States)

    The cDNA of the receptor for CAP2b/periviscerokinin (PVK) neuropeptides, designated Rhimi-CAP2b-R, was cloned from synganglia of tick Rhipicephalus (Boophilus) microplus. This receptor is the ortholog of the insect CAP2b/PVK receptor, as concluded from analyses of the predicted protein sequence, ph...

  13. Medullær thyroideacancer hos et ti måneder gammelt barn med multipel endokrin neoplasi 2B

    DEFF Research Database (Denmark)

    Mathiesen, Jes Sloth; Døssing, Helle; Bender, Lars;

    2014-01-01

    In infants at risk of multiple endocrine neoplasia type 2B (MEN2B) the American Thyroid Association recommends genetic testing as soon as possible after birth and that thyroidectomy should be performed in MEN2B RET-mutation positive individuals as soon as possible and if possible within the first...

  14. Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244).

    Science.gov (United States)

    Eissmann, Philipp; Beauchamp, Lisa; Wooters, Joe; Tilton, John C; Long, Eric O; Watzl, Carsten

    2005-06-15

    Triggering of 2B4 (CD244) can induce natural killer (NK)-cell activation, costimulation, or even inhibition of NK-cell activity. Here, we investigate the molecular basis for the different signals generated by 2B4. We show that the first immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of 2B4 is sufficient for 2B4-mediated NK-cell activation, whereas the third ITSM can negatively influence 2B4 signaling. We further identify signaling molecules that associate with 2B4. Signaling lymphocyte activation molecule-associated protein (SAP) can bind to all 4 ITSMs of 2B4 in a phosphorylation-dependent manner. The phosphorylated third ITSM can additionally recruit the phosphatases SHP-1, SHP-2, SHIP, and the inhibitory kinase Csk. SAP acts as an inhibitor of interactions between 2B4 and these negative regulatory molecules, explaining how 2B4 inhibits NK-cell activation in the absence of functional SAP, as occurs in cells from patients with X-linked lymphoproliferative syndrome (XLP). Recently, another function for SAP was proposed: SAP can recruit the kinase Fyn to the SLAM (CD150) immune receptor. We now show that Fyn can also associate with phosphorylated 2B4. Finally, we demonstrate that Fyn and Csk can both phosphorylate 2B4, suggesting a possible mechanism of 2B4 phosphorylation.

  15. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    Science.gov (United States)

    2010-04-01

    ... other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return information... regulations thereunder, including, if applicable, safeguards imposed by section 6103(p)(4). (d) Records...

  16. 76 FR 2930 - International Product Change-Global Plus 1B and 2B Negotiated Service Agreements

    Science.gov (United States)

    2011-01-18

    ... Product Change--Global Plus 1B and 2B Negotiated Service Agreements AGENCY: Postal Service \\TM\\. ACTION... add Global Plus 1B and 2B Negotiated Service Agreements to the Competitive Products List pursuant to... Service to Add Global Plus 1B and 2B Negotiated Service Agreements to the Competitive Product List, and...

  17. Li4Ge2B as a new derivative of the Mo2B5 and Li5Sn2 structure types.

    Science.gov (United States)

    Pavlyuk, Volodymyr; Ciesielski, Wojciech; Rozdzynska-Kielbik, Beata; Dmytriv, Grygoriy; Ehrenberg, Helmut

    2016-07-01

    Binary and multicomponent intermetallic compounds based on lithium and p-elements of Groups III-V of the Periodic Table are useful as modern electrode materials in lithium-ion batteries. However, the interactions between the components in the Li-Ge-B ternary system have not been reported. The structure of tetralithium digermanium boride, Li4Ge2B, exhibits a new structure type, in the noncentrosymmetric space group R3m, in which all the Li, Ge and B atoms occupy sites with 3m symmetry. The title structure is closely related to the Mo2B5 and Li5Sn2 structure types, which crystallize in the centrosymmetric space group R-3m. All the atoms in the title structure are coordinated by rhombic dodecahedra (coordination number = 14), similar to the atoms in related structures. According to electronic structure calculations using the tight-binding-linear muffin-tin orbital-atomic spheres approximation (TB-LMTO-ASA) method, strong covalent Ge-Ge and Ge-B interactions were established.

  18. CYP2B6*6 and CYP2B6*18 Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women.

    Science.gov (United States)

    Röhrich, Carola R; Drögemöller, Britt I; Ikediobi, Ogechi; van der Merwe, Lize; Grobbelaar, Nelis; Wright, Galen E B; McGregor, Nathaniel; Warnich, Louise

    2016-06-01

    Long-term exposure to efavirenz (EFV) measured in hair samples may predict response to antiretroviral treatment (ART). Polymorphisms in CYP2B6 are known to alter EFV levels. The aim of this study was to assess the relationship between CYP2B6 genotype, EFV levels measured in hair, and virological outcomes on ART in a real-world setting. We measured EFV levels in hair from HIV-positive South African females who had been receiving EFV-based treatment for at least 3 months from the South African Black (SAB) (n = 81) and Cape Mixed Ancestry (CMA) (n = 53) populations. Common genetic variation in CYP2B6 was determined in 15 individuals from each population using bidirectional Sanger sequencing. Prioritized variants (n = 16) were subsequently genotyped in the entire patient cohort (n = 134). The predictive value of EFV levels in hair and selected variants in CYP2B6 on virological treatment outcomes was assessed. Previously described alleles (CYP2B6*2, CYP2B6*5, CYP2B6*6, CYP2B6*17, and CYP2B6*18), as well as two novel alleles (CYP2B6*31 and CYP2B6*32), were detected in this study. Compared to noncarriers, individuals homozygous for CYP2B6*6 had ∼109% increased EFV levels in hair (p = .016) and CYP2B6*18 heterozygotes demonstrated 82% higher EFV hair levels (p = .0006). This study confirmed that alleles affecting CYP2B6 metabolism and subsequent EFV exposure are present at significant frequencies in both the SAB and CMA populations. Furthermore, this study demonstrated that the use of hair samples for testing EFV concentrations may be a useful tool in determining long-term drug exposure in resource-limited countries.

  19. MOLECULAR CLONING AND HETEROLOGOUS EXPRESSION OF HUMAN INTERFERON ALPHA2b GENE

    Directory of Open Access Journals (Sweden)

    I. Made Artika

    2013-01-01

    Full Text Available Human alpha Interferons (hIFNα have been shown to have antiviral, antiproliferative and immunomodulatory activities. The human interferon alpha2b (hIFNα2b, is one of the human interferon alpha2 sub variants, naturally synthesized as a polypeptide of 188 amino acid residues, the first 23 residues of which represents a signal peptide. In the present study, the hIFNα2b gene was expressed after being fused with Glutathione S-Transferase (GST gene. The hIFNα2b gene was amplified from human genomic DNA by using a pair of specific primers, cloned into an Escherichia coli expression vector and expressed in E. coli cells under the direction of the tac promoter. The expressed protein was purified using a one-step affinity chromatography column containing immobilized gluthatione-bound resin. The purified protein was shown to react specifically with anti-human-interferon-alpha antibody, confirming that the protein was the human interferon alpha molecule. This strategy has the potential to be used as an alternative mean for production of pure human interferon α proteins for therapeutic purposes and for further studies on their molecular characterization and mechanism of action.

  20. Johnston Atoll Site 2B-P 6/30/2000 7-8M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 7 and 8 meters along a permanent transect.

  1. Johnston Atoll Site 2B-P 6/30/2000 24-25M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 24 and 25 meters along a permanent transect.

  2. Johnston Atoll Site 2B-P 6/30/2000 37-38M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 37 and 38 meters along a permanent transect.

  3. Johnston Atoll Site 2B-P 6/30/2000 38-39M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 38 and 39 meters along a permanent transect.

  4. Improved Serodiagnosis of Cystic Echinococcosis Using the New Recombinant 2B2t Antigen

    Science.gov (United States)

    Hernández-González, Ana; Santivañez, Saúl; García, Héctor H.; Rodríguez, Silvia; Muñoz, Santiago; Ramos, Guillermo; Orduña, Antonio; Siles-Lucas, Mar

    2012-01-01

    A standardized test for the serodiagnosis of human cystic echinococcosis (CE) is still needed, because of the low specificity and sensitivity of the currently available commercial tools and the lack of proper evaluation of the existing recombinant antigens. In a previous work, we defined the new ELISA-B2t diagnostic tool for the detection of specific IgGs in CE patients, which showed high sensitivity and specificity, and was useful in monitoring the clinical evolution of surgically treated CE patients. Nevertheless, this recombinant antigen gave rise to false-negative results in a percentage of CE patients. Therefore, in an attempt to improve its sensitivity, we constructed B2t-derived recombinant antigens with two, four and eight tandem repeat of B2t units, and tested them by ELISA on serum samples of CE patients and patients with related parasites. The best diagnostic values were obtained with the two tandem repeat 2B2t antigen. The influence of several clinical variables on the performance of the tests was also evaluated. Finally, the diagnostic performance of the 2B2t-ELISA was compared with that of an indirect haemagglutination commercial test. The 2B2t recombinant antigen performed better than the HF and B2t antigens, and the IHA commercial kit. Therefore, this new 2B2t-ELISA is a promising candidate test for the serodiagnosis of CE in clinical settings. PMID:22802975

  5. One-pot synthesis of acenaphtho[1,2-b]furan derivatives

    Institute of Scientific and Technical Information of China (English)

    Mohammad Taghi Goldani; Reza Sandaroos; Saman Damavandi

    2012-01-01

    New 9-(alkyl or aryl)acenaphtho[ 1,2-b]furan-8-(alky or aryl)amine compounds has herein been reported by one-pot reaction of (acenaphthylen-l-yloxy)trimethylsilane,alkyl and aryl aldehydes,and aryl and alky isocyanides in refluxing DMF.

  6. 14 CFR Special Federal Aviation... - Mitsubishi MU-2B Series Special Training, Experience, and Operating Requirements

    Science.gov (United States)

    2010-01-01

    ... Balance A. Aircraft Loading Procedures B. Limitations 1. Weight Limits 2. C.G. Limits C. Plotter 1..., runway length, surface conditions, wind direction and velocity, brake heat energy, and any other... conditions. (c) No person may operate a Mitsubishi MU-2B series airplane unless a copy of the appropriate...

  7. Data of evolutionary structure change: 1DJ2B-1ADIB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DJ2B-1ADIB 1DJ2 1ADI B B IGSLSQVSGVLGCQWGDEGKGKLVDILAQHFDIVARCQG...LLSEACPLILDYHVALDNAREKARGAKAIGTTGRGIGPAYEDKVARRGLRVGDLFDKETFAEKLKEVMEYHNFQLVNYYKAEAVDYQKVLDDTMAVADI...LY CA 195 PHE CA 263 LYS CA 227 TYR CA 251 1ADI B 1ADIB 1 1ADI B 1ADI

  8. A Cross-Industry Review of B2B Critical Success Factors.

    Science.gov (United States)

    Eid, Riyad; Trueman, Myfanwy; Ahmed, Abdel Moneim

    2002-01-01

    Presents a comprehensive review of B2B (business-to- business) international Internet marketing and identifies 21 critical success factors in five categories: marketing strategy, including management support, strategic goals, and collaboration; Web site factors, including Web site design; global factors, including multilanguage sites and cultural…

  9. The 4W framework for B2B e-contracting

    NARCIS (Netherlands)

    Angelov, Samuil; Grefen, Paul

    2003-01-01

    Contracts are fundamental to the engagement of companies in commercial relations. B2B electronic contracting aims to improve the efficiency and effectiveness of the contracting process and to provide new opportunities for the contracting parties. Virtual enterprises, for example, can be dynamically

  10. A process-stakeholder analysis of B2B industry standardisation

    NARCIS (Netherlands)

    Rodon, J.; Ramis-Pujol, J.; Christiaanse, E.

    2007-01-01

    Purpose - Interoperability standards are a crucial aspect in the development of B2B e-business. The aim of this paper is to understand how standardisation evolves by analysing the interplay between activities and stakeholders within the process. Unlike most of the IS research that focuses on the und

  11. Using the Internet for B2B Activities: A Review and Future Directions for Research.

    Science.gov (United States)

    Gattiker, Urs E.; Perlusz, Stefano; Bohmann, Kristoffer

    2000-01-01

    Illustrates some of the challenges that electronic commerce practitioners and researchers face, focusing on business to business (B2B) transactions. Highlights include a conceptual framework of Web user behavior; purchasing context; socio-demographic characteristics; cultural factors; economic factors; attitudes toward information technology;…

  12. On the critical success factors for B2B e-marketplace

    Directory of Open Access Journals (Sweden)

    Sareh Ahmad Khan Beige

    2015-01-01

    Full Text Available Advancement of network technology, quick growth of Internet and Internet based solutions lead many firms to apply online processes as well as electronic businesses. Internet based B2B E-C requires applying Internet and affiliated technologies for exchanging products, services and information. Implementation of business to business (B2B requires long-term commitment of organizations. Carrying out research in this field is regarded as very important issue for recognizing effective factors on successful implementation and execution of B2B and determining current status of organization. This research deals with studying effective critical factors on successful implementation and execution of B2B. Factors are recognized through studying literature review and IT experts. Then, through case study (studying a vehicle manufacturing firm and by using analytical network process (ANP, the importance of factor and their rank are determined. The factors that are regarded at this research are including: culture, commitment and support of senior management, government support, purposes, organizational strategies, trust, partial advantage and technical infrastructure. Results of research show that support and commitment of senior management are the highest priority factors.

  13. Enabling low cost biopharmaceuticals: high level interferon alpha-2b production in Trichoderma reesei.

    Science.gov (United States)

    Landowski, Christopher P; Mustalahti, Eero; Wahl, Ramon; Croute, Laurence; Sivasiddarthan, Dhinakaran; Westerholm-Parvinen, Ann; Sommer, Benjamin; Ostermeier, Christian; Helk, Bernhard; Saarinen, Juhani; Saloheimo, Markku

    2016-06-10

    The filamentous fungus Trichoderma reesei has tremendous capability to secrete over 100 g/L of proteins and therefore it would make an excellent host system for production of high levels of therapeutic proteins at low cost. We have developed T. reesei strains suitable for production of therapeutic proteins by reducing the secreted protease activity. Protease activity has been the major hindrance to achieving high production levels. We have constructed a series of interferon alpha-2b (IFNα-2b) production strains with 9 protease deletions to gain knowledge for further strain development. We have identified two protease deletions that dramatically improved the production levels. Deletion of the subtilisin protease slp7 and the metalloprotease amp2 has enabled production levels of IFNα-2b up to 2.1 and 2.4 g/L, respectively. With addition of soybean trypsin protease inhibitor the level of production improved to 4.5 g/L, with an additional 1.8 g/L still bound to the secretion carrier protein. High levels of IFNα-2b were produced using T. reesei strains with reduced protease secretion. Further strain development can be done to improve the production system by reducing protease activity and improving carrier protein cleavage.

  14. An oxazolo[3,2-b]indazole route to 1H-indazolones.

    Science.gov (United States)

    Oakdale, James S; Solano, Danielle M; Fettinger, James C; Haddadin, Makhluf J; Kurth, Mark J

    2009-07-02

    The novel heterocycle 2,3-dihydrooxazolo[3,2-b]indazole has been synthesized and utilized to provide easy access to 1H-indazolones, particularly the previously unreported 2-(2-alkoxyethyl)-1H-indazol-3(2H)-ones. Mechanistic as well as optimization and reaction scope studies are reported.

  15. Johnston Atoll Site 2B-P 6/30/2000 14-15M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 14 and 15 meters along a permanent transect.

  16. Johnston Atoll Site 2B-P 6/30/2000 8-9M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 8 and 9 meters along a permanent transect.

  17. Johnston Atoll Site 2B-P 6/30/2000 6-7M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 6 and 7 meters along a permanent transect.

  18. Johnston Atoll Site 2B-P 6/30/2000 13-14M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 13 and 14 meters along a permanent transect.

  19. Johnston Atoll Site 2B-P 6/30/2000 27-28M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 27 and 28 meters along a permanent transect.

  20. Johnston Atoll Site 2B-P 6/30/2000 29-30M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 29 and 30 meters along a permanent transect.

  1. Johnston Atoll Site 2B-P 6/30/2000 2-3M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 2 and 3 meters along a permanent transect.

  2. Johnston Atoll Site 2B-P 6/30/2000 33-34M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 33 and 34 meters along a permanent transect.

  3. Johnston Atoll Site 2B-P 6/30/2000 26-27M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 26 and 27 meters along a permanent transect.

  4. Johnston Atoll Site 2B-P 6/30/2000 11-12M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 11 and 12 meters along a permanent transect.

  5. Johnston Atoll Site 2B-P 6/30/2000 3-4M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 3 and 4 meters along a permanent transect.

  6. Johnston Atoll Site 2B-P 6/30/2000 17-18M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 17 and 18 meters along a permanent transect.

  7. Johnston Atoll Site 2B-P 6/30/2000 5-6M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 5 and 6 meters along a permanent transect.

  8. Johnston Atoll Site 2B-P 6/30/2000 32-33M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 32 and 33 meters along a permanent transect.

  9. Johnston Atoll Site 2B-P 6/30/2000 35-36M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 35 and 36 meters along a permanent transect.

  10. Johnston Atoll Site 2B-P 6/30/2000 41-42M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 41 and 42 meters along a permanent transect.

  11. Hysteresis in the field-induced magnetic structure in TmNi2B2C

    DEFF Research Database (Denmark)

    Eskildsen, M.R.; Harada, K.; Gammel, P.L:

    1999-01-01

    Using small-angle neutron scattering we have studied the flux line lattice and the magnetic structure in TmNi2B2C. With an applied field parallel to the crystalline c-axis several magnetic and flux line lattice symmetry transitions have been reported. The subject of this paper is the held-induced...

  12. Structure and assembly of group B streptococcus pilus 2b backbone protein.

    Science.gov (United States)

    Cozzi, Roberta; Malito, Enrico; Lazzarin, Maddalena; Nuccitelli, Annalisa; Castagnetti, Andrea; Bottomley, Matthew J; Margarit, Immaculada; Maione, Domenico; Rinaudo, C Daniela

    2015-01-01

    Group B Streptococcus (GBS) is a major cause of invasive disease in infants. Like other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation mechanism to generate cell surface pili from backbone and ancillary pilin precursor substrates. The three pilus types identified in GBS contain structural subunits that are highly immunogenic and are promising candidates for the development of a broadly-protective vaccine. Here we report the X-ray crystal structure of the backbone protein of pilus 2b (BP-2b) at 1.06Å resolution. The structure reveals a classical IgG-like fold typical of the pilin subunits of other Gram-positive bacteria. The crystallized portion of the protein (residues 185-468) encompasses domains D2 and D3 that together confer high stability to the protein due to the presence of an internal isopeptide bond within each domain. The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire protein in conferring protection against GBS challenge in a well-established mouse model. By site-directed mutagenesis and complementation studies in GBS knock-out strains we identified the residues and motives essential for assembly of the BP-2b monomers into high-molecular weight complexes, thus providing new insights into pilus 2b polymerization.

  13. Structure and assembly of group B streptococcus pilus 2b backbone protein.

    Directory of Open Access Journals (Sweden)

    Roberta Cozzi

    Full Text Available Group B Streptococcus (GBS is a major cause of invasive disease in infants. Like other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation mechanism to generate cell surface pili from backbone and ancillary pilin precursor substrates. The three pilus types identified in GBS contain structural subunits that are highly immunogenic and are promising candidates for the development of a broadly-protective vaccine. Here we report the X-ray crystal structure of the backbone protein of pilus 2b (BP-2b at 1.06Å resolution. The structure reveals a classical IgG-like fold typical of the pilin subunits of other Gram-positive bacteria. The crystallized portion of the protein (residues 185-468 encompasses domains D2 and D3 that together confer high stability to the protein due to the presence of an internal isopeptide bond within each domain. The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire protein in conferring protection against GBS challenge in a well-established mouse model. By site-directed mutagenesis and complementation studies in GBS knock-out strains we identified the residues and motives essential for assembly of the BP-2b monomers into high-molecular weight complexes, thus providing new insights into pilus 2b polymerization.

  14. Johnston Atoll Site 2B-P 6/30/2000 4-5M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 4 and 5 meters along a permanent transect.

  15. Do self-service technologies affect interfirm relationships? A B2B perspective

    Directory of Open Access Journals (Sweden)

    Raechel Johns

    2014-11-01

    Full Text Available While considerable literature examines business-to business (B2B relationships, the impact of technology on these relationships has lacked attention. IT has impacted the way businesses operate in a B2B context as well as influencing services by altering the way services are delivered. To understand the way in which Internet technology has impacted these B2B services, it is essential to examine its impact not only on business processes but on business relationships too. One technology, enabled by modern Internet technologies, which is changing the nature of business relationships is the increased use of self-service technologies (SSTs or technology-enabled services, however, there is a shortage of research in the area in a B2B context. The discussion in this paper provides an overview of the impact of IT on business relationships, using Relationship Marketing theory to provide a theoretical framework. A qualitative study in the Australian banking industry provides findings relating to the theory. The findings of this study provide evidence that while traditional Relationship Marketing theory is still applicable for some business customers, new theory is required for business customers who do not seek relationships. With both practical and theoretical implications, the research detailed in this paper makes a useful contribution to the literature and indicates the necessity for further research to be developed which explores business customers who prefer to remain transaction-oriented, rather than develop interpersonal relationships.

  16. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  17. Johnston Atoll Site 2B-P 6/30/2000 12-13M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 12 and 13 meters along a permanent transect.

  18. Designing the marketing-sales interface in B2B firms

    NARCIS (Netherlands)

    Biemans, W.G.; Makovec Brencic, M.

    2007-01-01

    Purpose - This paper explores the marketing-sales interface in Dutch and Slovenian B2B firms. Design/methodology/approach - The study included 11 Dutch firms and ten Slovenian firms, with both samples as closely matched as possible. The firms were all manufacturers of physical products that operate

  19. Johnston Atoll Site 2B-P 6/30/2000 10-11M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 10 and 11 meters along a permanent transect.

  20. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2013

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Crane Creek. Water-Data Report 2013 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  1. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2014

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Crane Creek. Water-Data Report 2014 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  2. New High-Pressure Gallium Borate Ga2B3O7(OH) with Photocatalytic Activity.

    Science.gov (United States)

    Vitzthum, Daniela; Schauperl, Michael; Strabler, Christof M; Brüggeller, Peter; Liedl, Klaus R; Griesser, Ulrich J; Huppertz, Hubert

    2016-01-19

    The new high-pressure gallium borate Ga2B3O7(OH) was synthesized in a Walker-type multianvil apparatus under high-pressure/high-temperature conditions of 10.5 GPa and 700 °C. For the system Ga-B-O-H, it is only the second known compound next to Ga9B18O33(OH)15·H3B3O6·H3BO3. The crystal structure of Ga2B3O7(OH) was determined by single-crystal X-ray diffraction data collected at room temperature. Ga2B3O7(OH) crystallizes in the orthorhombic space group Cmce (Z = 8) with the lattice parameters a = 1050.7(2) pm, b = 743.6(2) pm, c = 1077.3(2) pm, and V = 0.8417(3) nm(3). Vibrational spectroscopic methods (Raman and IR) were performed to confirm the presence of the hydroxyl group. Furthermore, the band gap of Ga2B3O7(OH) was estimated via quantum-mechanical density functional theory calculations. These results led to the assumption that our gallium borate could be a suitable substance to split water photocatalytically, which was tested experimentally.

  3. A Cross-Industry Review of B2B Critical Success Factors.

    Science.gov (United States)

    Eid, Riyad; Trueman, Myfanwy; Ahmed, Abdel Moneim

    2002-01-01

    Presents a comprehensive review of B2B (business-to- business) international Internet marketing and identifies 21 critical success factors in five categories: marketing strategy, including management support, strategic goals, and collaboration; Web site factors, including Web site design; global factors, including multilanguage sites and cultural…

  4. Rapid protocol for visualization of rust fungi structures using fluorochrome Uvitex 2B.

    Science.gov (United States)

    Dugyala, Sheshanka; Borowicz, Pawel; Acevedo, Maricelis

    2015-01-01

    Histological examination using fluorochromes is one of the standard methods for observation of microorganisms in tissues and other compartments. In the study of fungi, especially those that cannot be cultured in axenic media such as biotrophic fungi, histological examination of processes associated with the fungal growth, differentiation, infection and other cellular functions can lead to the better understanding of host-parasite interactions. Fluorescence microscopy coupled with Fluorochrome Uvitex 2B have been extensively utilized to study rust fungi structures and host-pathogen interactions. In this study, we report development of a rapid staining protocol of the rust fungus Puccinia triticina using fluorochrome Uvitex 2B. The newly developed rapid procedure was compared with a standard staining technique to observe in planta fungal infection structures development during the wheat-Puccinia triticina interaction. While significantly reducing the time for staining, the rapid protocol described here was equally efficient or better compared to standard procedure in detecting fungal infection structures using Uvitex 2B. In the rapid staining procedure, pre-heating of the stain increased efficiency to detect all the infection structures including haustoria with highly reduced background noise from plant tissue. This staining process described here is simple and quick. It can be completed in 4 h, which is of 6 times faster than the standard Uvitex 2B staining procedure.

  5. genetic overexpression of NR2B subunit enhances social recognition memory for different strains and species.

    Directory of Open Access Journals (Sweden)

    Stephanie A Jacobs

    Full Text Available The ability to learn and remember conspecifics is essential for the establishment and maintenance of social groups. Many animals, including humans, primates and rodents, depend on stable social relationships for survival. Social learning and social recognition have become emerging areas of interest for neuroscientists but are still not well understood. It has been established that several hormones play a role in the modulation of social recognition including estrogen, oxytocin and arginine vasopression. Relatively few studies have investigated how social recognition might be improved or enhanced. In this study, we investigate the role of the NMDA receptor in social recognition memory, specifically the consequences of altering the ratio of the NR2B:NR2A subunits in the forebrain regions in social behavior. We produced transgenic mice in which the NR2B subunit of the NMDA receptor was overexpressed postnatally in the excitatory neurons of the forebrain areas including the cortex, amygdala and hippocampus. We investigated the ability of both our transgenic animals and their wild-type littermate to learn and remember juvenile conspecifics using both 1-hr and 24-hr memory tests. Our experiments show that the wild-type animals and NR2B transgenic mice preformed similarly in the 1-hr test. However, transgenic mice showed better performances in 24-hr tests of recognizing animals of a different strain or animals of a different species. We conclude that NR2B overexpression in the forebrain enhances social recognition memory for different strains and animal species.

  6. Construction of a 3D model of cytochrome P450 2B4.

    Science.gov (United States)

    Chang, Y T; Stiffelman, O B; Vakser, I A; Loew, G H; Bridges, A; Waskell, L

    1997-02-01

    A three-dimensional structural model of rabbit phenobarbital-inducible cytochrome P450 2B4 (LM2) was constructed by homology modeling techniques previously developed for building and evaluating a 3D model of the cytochrome P450choP isozyme. Four templates with known crystal structures including cytochrome P450cam, terp, BM-3 and eryF were used in multiple sequence alignments and construction of the cytochrome P450 2B4 coordinates. The model was evaluated for its overall quality using available protein analysis programs and found to be satisfactory. The model structure was stable at room temperature during a 140 ps unconstrained full protein molecular dynamics simulation. A putative substrate access channel and binding site were identified. Two different substrates, benzphetamine and androstenedione, that are metabolized by cytochrome P450 2B4 with pronounced product specificity were docked into the putative binding site. Two orientations were found for each substrate that could lead to the observed preferred products. Using a geometric fit method three regions on the surface of the model cytochrome P450 structure were identified as possible sites for interaction with cytochrome b5, a redox partner of P450 2B4. Residues that may interact with the substrates and with cytochrome b5 have been identified and mutagenesis studies are currently in progress.

  7. Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.

    Science.gov (United States)

    Densmore, John C; Schaid, Terry R; Jeziorczak, Paul M; Medhora, Meetha; Audi, Said; Nayak, Shraddha; Auchampach, John; Dwinell, Melinda R; Geurts, Aron M; Jacobs, Elizabeth R

    2017-02-01

    Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.

  8. Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo

    NARCIS (Netherlands)

    Vlaming, Hanneke; van Welsem, Tibor; de Graaf, Erik L; Ontoso, David; Altelaar, A F Maarten; San-Segundo, Pedro A; Heck, Albert J R; van Leeuwen, Fred

    2014-01-01

    Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 a

  9. Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo (Corrigendum)

    NARCIS (Netherlands)

    Vlaming, Hanneke; van Welsem, Tibor; de Graaf, Erik L; Ontoso, David; Altelaar, A F Maarten; San-Segundo, Pedro A; Heck, Albert J R; van Leeuwen, Fred

    2014-01-01

    Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 a

  10. An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

    Directory of Open Access Journals (Sweden)

    Rajeshwar Reddy Sagyam

    2009-11-01

    Full Text Available The reaction of 2-[2-(4-fluorophenyl-2-oxo-1-phenylethyl]-4-methyl-3-oxo-pentanoic acid phenylamide with tertiary butyl carbazate and subsequent condensation of the resulting carbamate derivative with a chalcone provided a facile new approach to pyrrolo[1,2-b]pyridazine derivatives.

  11. Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population

    Science.gov (United States)

    Takasaki, Yuto; Koide, Takayoshi; Wang, Chenyao; Kimura, Hiroki; Xing, Jingrui; Kushima, Itaru; Ishizuka, Kanako; Mori, Daisuke; Sekiguchi, Mariko; Ikeda, Masashi; Aizawa, Miki; Tsurumaru, Naoko; Iwayama, Yoshimi; Yoshimi, Akira; Arioka, Yuko; Yoshida, Mami; Noma, Hiromi; Oya-Ito, Tomoko; Nakamura, Yukako; Kunimoto, Shohko; Aleksic, Branko; Uno, Yota; Okada, Takashi; Ujike, Hiroshi; Egawa, Jun; Kuwabara, Hitoshi; Someya, Toshiyuki; Yoshikawa, Takeo; Iwata, Nakao; Ozaki, Norio

    2016-01-01

    N-methyl-d-aspartate receptors (NMDARs) play a critical role in excitatory synaptic transmission and plasticity in the central nervous systems. Recent genetics studies in schizophrenia (SCZ) show that SCZ is susceptible to NMDARs and the NMDAR signaling complex. In autism spectrum disorder (ASD), several studies report dysregulation of NMDARs as a risk factor for ASD. To further examine the association between NMDARs and SCZ/ASD development, we conducted a mutation screening study of GRIN2B which encodes NR2B subunit of NMDARs, to identify rare mutations that potentially cause diseases, in SCZ and ASD patients (n = 574 and 152, respectively). This was followed by an association study in a large sample set of SCZ, ASD, and normal healthy controls (n = 4145, 381, and 4432, respectively). We identified five rare missense mutations through the mutation screening of GRIN2B. Although no statistically significant association between any single mutation and SCZ or ASD was found, one of its variant, K1292R, is found only in the patient group. To further examine the association between mutations in GRIN2B and SCZ/ASD development, a larger sample size and functional experiments are needed. PMID:27616045

  12. The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells.

    Science.gov (United States)

    Wilson, Jeffrey M; Ross, William G; Agbai, Oma N; Frazier, Renea; Figler, Robert A; Rieger, Jayson; Linden, Joel; Ernst, Peter B

    2009-04-15

    The endogenous purine nucleoside adenosine is an important antiinflammatory mediator that contributes to the control of CD4(+) T cell responses. While adenosine clearly has direct effects on CD4(+) T cells, it remains to be determined whether actions on APC such as dendritic cells (DC) are also important. In this report we characterize DC maturation and function in BMDC stimulated with LPS in the presence or absence of the nonselective adenosine receptor agonist NECA (5'-N-ethylcarboxamidoadenosine). We found that NECA inhibited TNF-alpha and IL-12 in a concentration-dependent manner, whereas IL-10 production was increased. NECA-treated BMDC also expressed reduced levels of MHC class II and CD86 and were less effective at stimulating CD4(+) T cell proliferation and IL-2 production compared with BMDC exposed to vehicle control. Based on real-time RT-PCR, the A(2A) adenosine receptor (A(2A)AR) and A(2B)AR were the predominant adenosine receptors expressed in BMDC. Using adenosine receptor subtype selective antagonists and BMDC derived from A(2A)AR(-/-) and A(2B)AR(-/-)mice, it was shown that NECA modulates TNF-alpha, IL-12, IL-10, and CD86 responses predominantly via A(2B)AR. These data indicate that engagement of A(2B)AR modifies murine BMDC maturation and suggest that adenosine regulates CD4(+) T cell responses by selecting for DC with impaired immunogencity.

  13. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  14. Data of evolutionary structure change: 3EK2B-3FNFD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available rmsd> 3.226280927658081 EVID> 4 3FNF...3EK2B-3FNFD 3EK2 3FNF B D MGFLDGKRILLTGLLSNRSIAYGIAKACKREGAELAFTY...VGDRFKDRITEFAAEFGSE-LVFPCDVADDAQIDALFASLKTHWD---SLDGLVHSIGFAPREAIAG-DFLDGLTRENFRIAHDISAYSFPALAKAALPMLSDDASLL.../ss_2> EVID> 0 3EK2 3FNF D 3FNFD

  15. Textbook Evaluation: An Analysis of Listening Comprehension Parts in Top Notch 2A & 2B

    Science.gov (United States)

    Soori, Afshin; Haghani, Elham

    2015-01-01

    Textbooks are the instruments that assist both teachers and learners in process of second language learning. With respect to the importance of textbooks in a language course, evaluation of course books is a significant issue for most researchers. The present study investigated and analyzed Listening Comprehension parts in Top Notch 2A & 2B 2nd…

  16. First detection of canine parvovirus type 2b from diarrheic dogs in Himachal Pradesh

    Science.gov (United States)

    Sharma, Shalini; Dhar, Prasenjit; Thakur, Aneesh; Sharma, Vivek; Sharma, Mandeep

    2016-01-01

    Aim: The present study was conducted to detect the presence of canine parvovirus (CPV) among diarrheic dogs in Himachal Pradesh and to identify the most prevalent antigenic variant of CPV based on molecular typing and sequence analysis of VP2 gene. Materials and Methods: A total of 102 fecal samples were collected from clinical cases of diarrhea or hemorrhagic gastroenteritis from CPV vaccinated or non-vaccinated dogs. Samples were tested using CPV-specific polymerase chain reaction (PCR) targeting VP2 gene, multiplex PCR for detection of CPV-2a and CPV-2b antigenic variants, and a PCR for the detection of CPV-2c. CPV-2b isolate was cultured on Madin-Darby canine kidney (MDCK) cell lines and sequenced using VP2 structural protein gene. Multiple alignment and phylogenetic analysis was done using ClustalW and MEGA6 and inferred using the Neighbor-Joining method. Results: No sample was found positive for the original CPV strain usually present in the vaccine. However, about 50% (52 out of 102) of the samples were found to be positive with CPV-2ab PCR assay that detects newer variants of CPV circulating in the field. In addition, multiplex PCR assay that identifies both CPV-2ab and CPV-2b revealed that CPV-2b was the major antigenic variant present in the affected dogs. A PCR positive isolate of CPV-2b was adapted to grow in MDCK cells and produced characteristic cytopathic effect after 5th passage. Multiple sequence alignment of VP2 structural gene of CPV-2b isolate (Accession number HG004610) used in the study was found to be similar to other sequenced isolates in NCBI sequence database and showed 98-99% homology. Conclusion: This study reports the first detection of CPV-2b in dogs with hemorrhagic gastroenteritis in Himachal Pradesh and absence of other antigenic types of CPV. Further, CPV-specific PCR assay can be used for rapid confirmation of circulating virus strains under field conditions. PMID:27733797

  17. First detection of canine parvovirus type 2b from diarrheic dogs in Himachal Pradesh

    Directory of Open Access Journals (Sweden)

    Shalini Sharma

    2016-09-01

    Full Text Available Aim: The present study was conducted to detect the presence of canine parvovirus (CPV among diarrheic dogs in Himachal Pradesh and to identify the most prevalent antigenic variant of CPV based on molecular typing and sequence analysis of VP2 gene. Materials and Methods: A total of 102 fecal samples were collected from clinical cases of diarrhea or hemorrhagic gastroenteritis from CPV vaccinated or non-vaccinated dogs. Samples were tested using CPV-specific polymerase chain reaction (PCR targeting VP2 gene, multiplex PCR for detection of CPV-2a and CPV-2b antigenic variants, and a PCR for the detection of CPV-2c. CPV-2b isolate was cultured on Madin-Darby canine kidney (MDCK cell lines and sequenced using VP2 structural protein gene. Multiple alignment and phylogenetic analysis was done using ClustalW and MEGA6 and inferred using the Neighbor-Joining method. Results: No sample was found positive for the original CPV strain usually present in the vaccine. However, about 50% (52 out of 102 of the samples were found to be positive with CPV-2ab PCR assay that detects newer variants of CPV circulating in the field. In addition, multiplex PCR assay that identifies both CPV-2ab and CPV-2b revealed that CPV-2b was the major antigenic variant present in the affected dogs. A PCR positive isolate of CPV-2b was adapted to grow in MDCK cells and produced characteristic cytopathic effect after 5th passage. Multiple sequence alignment of VP2 structural gene of CPV-2b isolate (Accession number HG004610 used in the study was found to be similar to other sequenced isolates in NCBI sequence database and showed 98-99% homology. Conclusion: This study reports the first detection of CPV-2b in dogs with hemorrhagic gastroenteritis in Himachal Pradesh and absence of other antigenic types of CPV. Further, CPV-specific PCR assay can be used for rapid confirmation of circulating virus strains under field conditions.

  18. Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

    Energy Technology Data Exchange (ETDEWEB)

    Peters, L.M.; Demmel, S. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Pusch, G.; Buters, J.T.M. [ZAUM — Center of Allergy and Environment, Helmholtz Zentrum München/Technische Universität München, Biedersteiner Str. 29, 80802 München (Germany); Thormann, W. [Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Murtenstrasse 35, 3010 Bern (Switzerland); Zielinski, J. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Leeb, T. [Institute of Genetics, Vetsuisse Faculty, University Bern, Bremgartenstr. 109, 3012 Bern (Switzerland); Mevissen, M. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Schmitz, A., E-mail: andrea.schmitz@vetsuisse.unibe.ch [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland)

    2013-01-01

    Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V{sub max} for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and K{sub m} was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC{sub 50} of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP

  19. Experiment data report for Semiscale Mod-1 tests S-05-2A and S-05-2B (alternate ECC injection tests)

    Energy Technology Data Exchange (ETDEWEB)

    Patton, Jr., M. L.; Collins, B. L.; Sackett, K. E.

    1977-04-01

    Recorded test data are presented for Tests S-05-2A and S-05-2B of the Semiscale Mod-1 alternate ECC injection test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Tests S-05-2A and S-05-2B were conducted from initial conditions of 2263 psia and 543/sup 0/F and 2272 psia and 542/sup 0/F, respectively, to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the cold leg broken loop piping. During the tests, cooling water was injected into the intact loop pump suction and broken loop cold leg to simulate emergency core coolant injection in a PWR with flow rates based on system volume scaling. For Test S-05-2A the intact loop pump speed was held constant throughout the test at the initial blowdown value. During Test S-05-2B the pump speed was reduced and stopped according to a predetermined coastdown schedule.

  20. Uso de una conantokina y anticuerpos policlonales para identificar la subunidad NR2B del receptor

    Directory of Open Access Journals (Sweden)

    Leonardo Lareo,†

    2010-12-01

    Full Text Available Objetivo. Proponer una metodología de identificación de la subunidad NR2B, mediante el uso de conantokina G, así como una adecuada extracción de la subunidad NR2B. Materiales y métodos. Se ensayaron dos metodologías para la extracción de la subunidad NR2B de cerebro de rata adulta, la primera buscó la extracción de la subunidad a partir de la membrana mediante la utilización del detergente deoxicolato de sodio y la segunda, garantizó primero la solubilización y eliminación de proteínas citoplasmáticas para luego realizar la extracción de la subunidad mediante el uso del mismo detergente, a partir del pellet generado en la centrifugación del extracto obtenido. Adicionalmente se biotiniló la conantokina G para evaluar su eficiencia en la identificación de la subunidad y comparar los resultados con los obtenidos por metodologías tradicionales como DOT-BLOT, WESTERN-BLOT, ELISA e Inmunohistoquímica. Resultados. La segunda metodología mostró mayor extracción de NR2B por lo que se seleccionó para la realización de los extractos posteriores. Los ensayos de identificación con la conantokina biotinilada evidenciaron interferencia en el reconocimiento, haciéndose necesaria la identificación de la presencia de la subunidad NR2B mediante el uso de anticuerpos policlonales en los ensayos mencionados. Conclusiones. Se propone que hay un impedimento de tipo estérico en el marcaje de la conantokina con la biotina lo que no favorece la interacción de este péptido con la subunidad.

  1. Estrogen receptor 2b deficiency impairs the antiviral response of zebrafish.

    Science.gov (United States)

    López-Muñoz, Azucena; Liarte, Sergio; Gómez-González, Nuria E; Cabas, Isabel; Meseguer, José; García-Ayala, Alfonsa; Mulero, Victoriano

    2015-11-01

    Although several studies have demonstrated the ability of some endocrine disruptive chemicals (EDCs) to alter the physiology of zebrafish, the immune-reproductive interaction has received little attention in this species. In this study, we used a homozygous line carrying an insertion of 8 amino acids in the ligand-binding domain of the estrogen receptor 2b gene (esr2b) to further understand the role of estrogen signaling on innate immunity. Adult mutant fish showed distorted sexual ratios related with alterations in testicular morphology and supraphysiological testosterone and 17β-estradiol (E2) levels. Immunity-wise, although esr2b mutant fish showed unaltered antibacterial responses, they were unable to mount an effective antiviral response upon viral challenge. RT-qPCR analysis demonstrated that mutant fish were able to induce the genes encoding major antiviral molecules, including Ifnphi1, Ifnphi2, Infphi3, Mxb and Mxc, and the negative feedback regulator of cytokine signaling Socs1. Notably, although esr2b mutant larvae showed a similar resistance to SVCV infection to their wild type siblings, waterborne E2 increased their viral susceptibility. Similarly, the exposure of adult wild type zebrafish to E2 also resulted in increased susceptibility to SVCV infection. Finally, the administration of recombinant Ifnphi1 hardly reversed the higher viral susceptibility of esr2b mutant zebrafish, suggesting that elevated socs1 levels impair Ifn signaling. All together, these results uncover an important role for E2 and Esr signaling in the fine-tuning of sexual hormone balance and the antiviral response of vertebrates.

  2. Atmospheric circulation of eccentric hot Jupiter HAT-P-2B

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Nikole K. [Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Showman, Adam P. [Department of Planetary Sciences and Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Marley, Mark S., E-mail: nklewis@mit.edu [NASA Ames Research Center 245-3, Moffett Field, CA 94035 (United States)

    2014-11-10

    The hot Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full orbit phase curves at 3.6, 4.5 and 8.0 μm, which is likely due to a chemical process not captured by our current atmospheric models for HAT-P-2b. Further modeling and observational efforts focused on understanding the chemistry of HAT-P-2b's atmosphere are needed and could provide key insights into the interplay between radiative, dynamical, and chemical processes in a wide range of exoplanet atmospheres.

  3. The International Space Station 2B Photovoltaic Thermal Control System (PVTCS) Leak: An Operational History

    Science.gov (United States)

    Vareha, Anthony N.

    2014-01-01

    As early as 2004, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B electrical power channel began slowly leaking ammonia overboard. Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity (EVA) during the STS-134 Space Shuttle mission. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. In mid-2012, the leak rate increased from 1.5lbm/year to approximately 5lbm/year. As a result, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to an adjacent dormant thermal control system. This EVA, US EVA 20, was successfully executed on November 1, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a different radiator than what the system was designed to utilize. Data monitoring over the next several months showed that the isolated radiator had not been leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the crew noticing the leak, US EVA 21 was in progress to replace the coolant pump - the only remaining replaceable leak source. This was successful, and telemetry monitoring has shown that indeed the coolant pump was the leak source and was thus isolated from the running 2B PVTCS. This paper will explore the management of the 2B PVTCS leak from the operations perspective.

  4. Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor.

    Science.gov (United States)

    Kohalmy, Krisztina; Tamási, Viola; Kóbori, László; Sárváry, Eniko; Pascussi, Jean-Marc; Porrogi, Pálma; Rozman, Damjana; Prough, Russell A; Meyer, Urs A; Monostory, Katalin

    2007-09-01

    Dehydroepiandrosterone (DHEA), the major precursor of androgens and estrogens, has several beneficial effects on the immune system, on memory function, and in modulating the effects of diabetes, obesity, and chemical carcinogenesis. Treatment of rats with DHEA influences expression of cytochrome P450 (P450) genes, including peroxisome proliferator-activated receptor alpha (PPAR alpha)- and pregnane X receptor (PXR)-mediated induction of CYP4As and CYP3A23, and suppression of CYP2C11. DHEA treatment elevated the expression and activities of CYP3A4, CYP2C9, CYP2C19, and CYP2B6 in primary cultures of human hepatocytes. Induction of CYP3A4 in human hepatocytes was consistent with studies in rats, but induction of CYP2Cs was unexpected. The role of PXR in this response was studied in transient transfection assays. DHEA activated hPXR in a concentration-dependent manner. Because CYP2B6 induction by DHEA in human hepatocytes might involve either PXR or constitutive androstane receptor (CAR) activation, we performed experiments in primary hepatocytes from CAR knockout mice and observed that CAR was required for maximal induction of Cyp2b10 by DHEA. Furthermore, CAR-mediated Cyp2b10 induction by DHEA was inhibited by the inverse agonist of CAR, androstanol (5 alpha-androstan-3 alpha-ol). Further evidence for CAR activation was provided by cytoplasmic/nuclear transfer of CAR upon DHEA treatment. Elucidation of CAR activation and subsequent induction of CYP2B6 by DHEA presented an additional mechanism by which the sterol can modify the expression of P450s. The effect of DHEA on the activation of the xenosensors PPAR alpha, PXR, and CAR, and the consequent potential for adverse drug/toxicant interactions should be considered in humans treated with this nutriceutical agent.

  5. Nematode and arthropod genomes provide new insights into the evolution of class 2 B1 GPCRs.

    Directory of Open Access Journals (Sweden)

    João C R Cardoso

    Full Text Available Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs. Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.

  6. Prostate cancer pathologic stage pT2b (2002 TNM staging system: does it exist?

    Directory of Open Access Journals (Sweden)

    Maisa M. Quintal

    2006-02-01

    Full Text Available OBJECTIVE: In the 1997 TNM staging system, tumors were classified into a single subdivision: T2a, and bilateral tumor involvement (T2b. In the 2002 TNM staging system, tumors are subclassified as T2a (less than one half of one lobe involvement, T2b (more than one half of one lobe involvement, and T2c (bilateral involvement. A recent study questioned the existence of a true pathologic pT2b tumor. The aim of our study is to verify this question. MATERIALS AND METHODS: The study population consisted of 224 men submitted to radical retropubic prostatectomy. The surgical specimens were histologically evaluated by complete embedding and whole-mount processing. Tumor extent was evaluated by a point-count method. The surgical specimens were staged according to the 2002 TNM staging system. RESULTS: Using the 2002 TNM criteria, the surgical specimens were classified as pT2a, 28 (12.50%; pT2b, 0 (0%; pT2c, 138 (61.61%; pT3a, 30 (13.39%; and, pT3b, 28 (12.50%. Using the point-count method for tumor extent evaluation, the minimum and maximum total points obtained in unilateral tumors were 192 and 368 points, respectively; the most extensive unilateral tumor showed 68 positive points (less than half the minimum total point-count. CONCLUSIONS: Using the point-count method for tumor extent, our study questions a real existence for pathologic stage pT2b tumors (unilateral tumors involving greater than one-half of one lobe.

  7. GRIN2B Mutations in West Syndrome and Intellectual Disability with Focal Epilepsy

    Science.gov (United States)

    Lemke, Johannes R; Hendrickx, Rik; Geider, Kirsten; Laube, Bodo; Schwake, Michael; Harvey, Robert J; James, Victoria M; Pepler, Alex; Steiner, Isabelle; Hörtnagel, Konstanze; Neidhardt, John; Ruf, Susanne; Wolff, Markus; Bartholdi, Deborah; Caraballo, Roberto; Platzer, Konrad; Suls, Arvid; De Jonghe, Peter; Biskup, Saskia; Weckhuysen, Sarah

    2014-01-01

    Objective To identify novel epilepsy genes using a panel approach and describe the functional consequences of mutations. Methods Using a panel approach, we screened 357 patients comprising a vast spectrum of epileptic disorders for defects in genes known to contribute to epilepsy and/or intellectual disability (ID). After detection of mutations in a novel epilepsy gene, we investigated functional effects in Xenopus laevis oocytes and screened a follow-up cohort. Results We revealed de novo mutations in GRIN2B encoding the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor in 2 individuals with West syndrome and severe developmental delay as well as 1 individual with ID and focal epilepsy. The patient with ID and focal epilepsy had a missense mutation in the extracellular glutamate-binding domain (p.Arg540His), whereas both West syndrome patients carried missense mutations within the NR2B ion channel-forming re-entrant loop (p.Asn615Ile, p.Val618Gly). Subsequent screening of 47 patients with unexplained infantile spasms did not reveal additional de novo mutations, but detected a carrier of a novel inherited GRIN2B splice site variant in close proximity (c.2011-5_2011-4delTC). Mutations p.Asn615Ile and p.Val618Gly cause a significantly reduced Mg2+ block and higher Ca2+ permeability, leading to a dramatically increased Ca2+ influx, whereas p.Arg540His caused less severe disturbance of channel function, corresponding to the milder patient phenotype. Interpretation We identified GRIN2B gain-of-function mutations as a cause of West syndrome with severe developmental delay as well as of ID with childhood onset focal epilepsy. Severely disturbed channel function corresponded to severe clinical phenotypes, underlining the important role of facilitated NMDA receptor signaling in epileptogenesis. PMID:24272827

  8. Effects of maternal enflurane exposure on NR2B expression in the hippocampus of their offspring

    Directory of Open Access Journals (Sweden)

    Fo-Quan Luo

    2015-09-01

    Full Text Available This work aims to study the pathogenesis of learning and memory impairment in offspring rats resulting from maternal enflurane anesthesia by focusing on the expression of the N-methyl-d-aspartic acid receptor subunit 2B (NR2B in the hippocampus of the offspring. Thirty female Sprague-Dawley rats were randomly divided into three groups: control (C group, 4 h enflurane exposure (E1 group, and 8 h enflurane exposure (E2 group groups. Eight to ten days after the initiation of pregnancy, rats from the E1 and E2 groups were allowed to inhale 1.7% enflurane in 2 L/min oxygen for 4 h and 8 h, respectively. Rats from the C group were allowed to inhale 2 L/min of oxygen only. The Morris water maze was used to assay the learning and memory function of the offspring on postnatal days 20 and 30. RT-PCR and immunohistochemistry assays were then used to measure the mRNA levels and protein expression of NR2B, respectively. Relative to offspring rats from the C group, those from the E1 and E2 groups exhibited longer escape latencies, lesser number of crossings over the platform, and less time spent in the target quadrant in the spatial exploration test (P 0.05 in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression.

  9. Using msa-2b as a molecular marker for genotyping Mexican isolates of Babesia bovis.

    Science.gov (United States)

    Genis, Alma D; Perez, Jocelin; Mosqueda, Juan J; Alvarez, Antonio; Camacho, Minerva; Muñoz, Maria de Lourdes; Rojas, Carmen; Figueroa, Julio V

    2009-12-01

    Variable merozoite surface antigens of Babesia bovis are exposed glycoproteins having a role in erythrocyte invasion. Members of this gene family include msa-1 and msa-2 (msa-2c, msa-2a(1), msa-2a(2) and msa-2b). To determine the sequence variation among B. bovis Mexican isolates using msa-2b as a genetic marker, PCR amplicons corresponding to msa-2b were cloned and plasmids carrying the corresponding inserts were purified and sequenced. Comparative analysis of nucleotide and deduced amino acid sequences revealed distinct degrees of variability and identity among the coding gene sequences obtained from 16 geographically different Mexican B. bovis isolates and a reference strain. Clustal-W multiple alignments of the MSA-2b deduced amino acid sequences performed with the 17 B. bovis Mexican isolates, revealed the identification of three genotypes with a distinct set each of amino acid residues present at the variable region: Genotype I represented by the MO7 strain (in vitro culture-derived from the Mexico isolate) as well as RAD, Chiapas-1, Tabasco and Veracruz-3 isolates; Genotype II, represented by the Jalisco, Mexico and Veracruz-2 isolates; and Genotype III comprising the sequences from most of the isolates studied, Tamaulipas-1, Chiapas-2, Guerrero-1, Nayarit, Quintana Roo, Nuevo Leon, Tamaulipas-2, Yucatan and Guerrero-2. Moreover, these three genotypes could be discriminated against each other by using a PCR-RFLP approach. The results suggest that occurrence of indels within the variable region of msa-2b sequences can be useful markers for identifying a particular genotype present in field populations of B. bovis isolated from infected cattle in Mexico.

  10. Cumene hydroperoxide-supported demethylation reactions catalyzed by cytochrome P450 2B4 lacking the NH2-terminal sequence.

    Science.gov (United States)

    Zhang, Y; Pernecky, S J

    1999-04-29

    Catalytic activities of cytochrome P450 2B4 lacking NH2-terminal amino acids 2-27 (wt Delta2B4) and that of truncated 2B4 containing a Pro to Ser mutation at position 221 were examined in a system supported by cumene hydroperoxide. Demethylation activities of either truncated 2B4 with N-methylaniline, N,N-dimethylaniline, and d-benzphetamine were lower than those of liver microsomal 2B4, whereas the rate of 1-phenylethanol oxidation to acetophenone catalyzed by liver microsomal and truncated 2B4 enzymes was nearly the same. The Km and Vmax values for cumene hydroperoxide in the demethylation of N-methylaniline by wt Delta2B4 were 20% and 28%, respectively, of those obtained for 2B4. The reaction with wt Delta2B4 displayed a lesser dependence on phospholipid than did that with 2B4, and a complex relationship between activity and substrate concentration. The results suggest that the NH2-terminal region contributes to interaction of oxidant, substrate, and phospholipid in cumene hydroperoxide-supported reactions catalyzed by cytochrome P450 2B4.

  11. Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor.

    Science.gov (United States)

    Yueh, M F; Mellon, P L; Tukey, R H

    2011-06-01

    The xenobiotic receptors, constitutive androstane receptor (CAR), and pregnane X receptor (PXR) regulate and alter the metabolism of xenobiotic substrates. Among the 19 functional UDP-glucuronosyltransferases (UGTs) in humans, UGT2B7 is involved in the metabolism of many structurally diverse xenobiotics and plays an important role in the clearance and detoxification of many therapeutic drugs. To examine whether this gene is regulated by CAR and PXR in vivo, transgenic mice expressing the entire UGT2B7 gene (TgUGT2B7) were created. Gene expression profiles revealed that UGT2B7 is differentially expressed in liver, kidney, adipocytes, brain, and estrogen-sensitive tissues, such as ovary and uterus. Liver UGT2B7 expression levels were decreased when TgUGT2B7 mice were treated with the CAR ligand 1,4-b-s-[2-(3,5,-dichloropyridyloxy)] (TCPOBOP) but not the PXR ligand pregnenolone 16α-carbonitrile. Although TCPOBOP decreased the levels of UGT2B7 mRNA in TgUGT2B7 mice, it had no affect on Tg(UGT2B7)Car(-/-) mice, adding support for a CAR-dependent mechanism contributing toward UGT2B7 gene suppression. Expression of promoter constructs in HepG2 cells showed the CAR-dependent inhibition was linked to hepatocyte nuclear factor-4α (HNF4α)-mediated transactivation of the UGT2B7 promoter. The inhibitory effect of CAR on UGT2B7 gene expression was validated in chromatin immunoprecipitation assays in which TCPOBOP treatment blocked HNF4α binding to the UGT2B7 promoter. These results suggest that HNF4α plays an important role in the constitutive expression of hepatic UGT2B7, and CAR acts as a negative regulator by interfering with HNF4α binding activity.

  12. Dynamics of the formation and loss of boron atoms in a H2/B2H6 microwave plasma

    Science.gov (United States)

    Duluard, C. Y.; Aubert, X.; Sadeghi, N.; Gicquel, A.

    2016-09-01

    For further improvements in doped-diamond deposition technology, an understanding of the complex chemistry in H2/CH4/B2H6 plasmas is of general importance. In this context, a H2/B2H6 plasma ignited by microwave power in a near resonant cavity at high pressure (100-200 mbar) is studied to measure the B-atom density in the ground state. The discharge is ignited in the gas mixture (0-135 ppm B2H6 in H2) by a 2.45 GHz microwave generator, leading to the formation of a hemispheric plasma core, surrounded by a faint discharge halo filling the remaining reactor volume. Measurements with both laser induced fluorescence and resonant absoption with a boron hollow cathode lamp indicate that the B-atom density is higher in the halo than in the plasma core. When the absorption line-of-sight is positioned in the halo, the absorption is so strong that the upper detection limit is reached. To understand the mechanisms of creation and loss of boron atoms, time-resolved absorption measurements have been carried out in a pulsed plasma regime (10 Hz, duty cycle 50%). The study focuses on the influence of the total pressure, the partial pressure of B2H6, as well as the source power, on the growth and decay rates of boron atoms when the plasma is turned off.

  13. Renormalized Volume

    Science.gov (United States)

    Gover, A. Rod; Waldron, Andrew

    2017-09-01

    We develop a universal distributional calculus for regulated volumes of metrics that are suitably singular along hypersurfaces. When the hypersurface is a conformal infinity we give simple integrated distribution expressions for the divergences and anomaly of the regulated volume functional valid for any choice of regulator. For closed hypersurfaces or conformally compact geometries, methods from a previously developed boundary calculus for conformally compact manifolds can be applied to give explicit holographic formulæ for the divergences and anomaly expressed as hypersurface integrals over local quantities (the method also extends to non-closed hypersurfaces). The resulting anomaly does not depend on any particular choice of regulator, while the regulator dependence of the divergences is precisely captured by these formulæ. Conformal hypersurface invariants can be studied by demanding that the singular metric obey, smoothly and formally to a suitable order, a Yamabe type problem with boundary data along the conformal infinity. We prove that the volume anomaly for these singular Yamabe solutions is a conformally invariant integral of a local Q-curvature that generalizes the Branson Q-curvature by including data of the embedding. In each dimension this canonically defines a higher dimensional generalization of the Willmore energy/rigid string action. Recently, Graham proved that the first variation of the volume anomaly recovers the density obstructing smooth solutions to this singular Yamabe problem; we give a new proof of this result employing our boundary calculus. Physical applications of our results include studies of quantum corrections to entanglement entropies.

  14. Photoelectron Spectroscopy Study of [Ta2B6]-: a Hexagonal Bipyramdial Cluster

    Science.gov (United States)

    Jian, Tian; Li, Weili; Romanescu, Constantin; Wang, Lai-Sheng

    2014-06-01

    It has been a long-sought goal in cluster science to discover stable atomic clusters as building blocks for cluster-assembled nanomaterials, as exemplified by the fullerenes and their subsequent bulk syntheses.[1,2] Clusters have also been considered as models to understand bulk properties, providing a bridge between molecular and solid-state chemistry.[3] Herein we report a joint photoelectron spectroscopy and theoretical study on the [Ta2B6]- and [Ta2B6] clusters.[4] The photoelectron spectrum of [Ta2B6]- displays a simple spectral pattern and a large HOMO-LUMO gap, suggesting its high symmetry. Theoretical calculations show that both the neutral and anion are D6h pyramidal. The chemical bonding analyses for [Ta2B6] revealed the nature of the B6 and Ta interactions and uncovered strong covalent bonding between B6 and Ta. The D6h-[TaB6Ta] gaseous cluster is reminiscent of the structural pattern in the ReB6X6Re core in the [(Cp*Re)2B6H4Cl2] and the TiB6Ti motif in the newly synthesized Ti7Rh4Ir2B8 solid-state compound.[5,6] The current work provides an intrinsic link between a gaseous cluster and motifs for solid materials. Continued investigations of the transition-metal boron clusters may lead to the discovery of new structural motifs involving pure boron clusters for the design of novel boride materials. Reference [1] H.W. Kroto, J. R. Heath, S. C. OBrien, R. F. Curl, R. E. Smalley, Nature 1985, 318, 162 - 163. [2] W. Krtschmer, L. D. Lamb, K. Fostiropoulos, D. R. Huffman, Nature 1990, 347, 354 - 358. [3] T. P. Fehlner, J.-F. Halet, J.-Y. Saillard, Molecular Clusters: A Bridge to Solid-State Chemitry, Cambridge University Press, UK, 2007. [4] W. L. Li, L. Xie, T. Jian, C. Romanescu, X. Huang, L.-S. Wang, Angew. Chem. Int. Ed. 2014, 126, 1312 - 1316. [5] B. Le Guennic, H. Jiao, S. Kahlal, J.-Y. Saillard, J.-F. Halet, S. Ghosh, M. Shang, A. M. Beatty, A. L. Rheingold, T. P. Fehlner, J. Am. Chem. Soc. 2004, 126, 3203 - 3217. [6] B. P. T. Fokwa, M. Hermus, Angew

  15. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

  16. Reaction and reorientation of electronically excited H{sub 2}(B)

    Energy Technology Data Exchange (ETDEWEB)

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H{sub 2}, HD, and D{sub 2} B {sup 1}{Sigma}{sub u}{sup +} by {sup 4}He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H{sub 2}, HD and D{sub 2} (B {sup 1}{Sigma}{sub u}{sup +}. v{prime}=0, J{prime}=1, M{sub J}=0) in collisions with He, Ne, Ar and H{sub 2}(X {sup 1}{Sigma}{sub g}{sup +}) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250{plus_minus}40 cm{sup {minus}1}, and the difference in the H-H stretching frequencies between H{sub 2}(B) and the H{sub 2}-He complex at the barrier to reaction is 140{plus_minus}80 cm{sup {minus}1}. The effective cross sections for angular momentum reorientation in collisions of H{sub 2}, HD, D{sub 2} with He and Ne were found to be about 30 {Angstrom}{sup 2} and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D{sub 2} in collisions with Ar were 10.6{plus_minus}2.0 and 13.9{plus_minus}3.0 {Angstrom}{sup 2}, respectively. Reorientation of D{sub 2}(B) in collisions with room temperature H{sub 2}(X) occurs with a 7.6{plus_minus}3.4 {Angstrom}{sup 2} cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H{sub 2}(B) and D{sub 2}(B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  17. Reaction and reorientation of electronically excited H[sub 2](B)

    Energy Technology Data Exchange (ETDEWEB)

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H[sub 2], HD, and D[sub 2] B [sup 1][Sigma][sub u][sup +] by [sup 4]He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H[sub 2], HD and D[sub 2] (B [sup 1][Sigma][sub u][sup +]. v[prime]=0, J[prime]=1, M[sub J]=0) in collisions with He, Ne, Ar and H[sub 2](X [sup 1][Sigma][sub g][sup +]) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250[plus minus]40 cm[sup [minus]1], and the difference in the H-H stretching frequencies between H[sub 2](B) and the H[sub 2]-He complex at the barrier to reaction is 140[plus minus]80 cm[sup [minus]1]. The effective cross sections for angular momentum reorientation in collisions of H[sub 2], HD, D[sub 2] with He and Ne were found to be about 30 [Angstrom][sup 2] and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D[sub 2] in collisions with Ar were 10.6[plus minus]2.0 and 13.9[plus minus]3.0 [Angstrom][sup 2], respectively. Reorientation of D[sub 2](B) in collisions with room temperature H[sub 2](X) occurs with a 7.6[plus minus]3.4 [Angstrom][sup 2] cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H[sub 2](B) and D[sub 2](B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  18. Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes.

    Science.gov (United States)

    Bae, Soo Hyeon; Kwon, Min Jo; Choi, Eu Jin; Zheng, Yu Fen; Yoon, Kee Dong; Liu, Kwang-Hyeon; Bae, Soo Kyung

    2013-09-05

    The present study was performed to evaluate the potency and specificity of sibutramine as an inhibitor of the activities of nine human CYP isoforms in liver microsomes. Using a cocktail assay, the effects of sibutramine on specific marker reactions of the nine CYP isoforms were measured in human liver microsomes. Sibutramine showed potent inhibition of CYP2B6-mediated bupropion 6-hydroxylation with an IC50 value of 1.61μM and Ki value of 0.466μM in a competitive manner at microsomal protein concentrations of 0.25mg/ml; this was 3.49-fold more potent than the typical CYP2B6 inhibitor thio-TEPA (Ki=1.59μM). In addition, sibutramine slightly inhibited CYP2C19 activity (Ki=16.6μM, noncompetitive inhibition) and CYP2D6 activity (Ki=15.7μM, noncompetitive inhibition). These observations indicated 35.6- and 33.7-fold decreases in inhibition potency, respectively, compared with that of CYP2B6 by sibutramine. However, no inhibition of CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, or CYP2E1 activities was observed. In addition, the CYP2B6 inhibitory potential of sibutramine was enhanced at a lower microsomal protein concentration of 0.05mg/ml. After 30min preincubation of human liver microsomes with sibutramine in the presence of NADPH, no shift in IC50 was observed in terms of inhibition of the activities of the nine CYPs, suggesting that sibutramine is not a time-dependent inactivator. These observations suggest that sibutramine is a selective and potent inhibitor of CYP2B6 in vitro, whereas inhibition of other CYPs is substantially lower. These in vitro data support the use of sibutramine as a well-known inhibitor of CYP2B6 for routine screening of P450 reversible inhibition when human liver microsomes are used as the enzyme source.

  19. Cmv2b-AGO interaction is required for the suppression of RDR-dependent antiviral silencing in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Fang

    2016-08-01

    Full Text Available Using a transient plant system, it was previously found that the suppression of Cucumber mosaic virus (CMV 2b protein relies on its double-strand (ds RNA binding capacity, but it is independent of its interaction with ARGONAUTE (AGO proteins. Thus, the biological meaning of the 2b-AGO interaction in the context of virus infection remains elusive. In this study, we created infectious clones of CMV mutants that expressed the 2b functional domains of dsRNA or AGO binding and tested the effect of these CMV mutants on viral pathogenicity. We found that the mutant CMV2b(1-76 expressing the 2b dsRNA-binding domain exhibited the same virulence as wild-type CMV in infection with either wild-type Arabidopsis or rdr1/6 plants with RDR1- and RDR6-deficient mutations. However, remarkably reduced viral RNA levels and increased virus (vsiRNAs were detected in CMV2b(1-76-infected Arabidopsis in comparison to CMV infection, which demonstrated that the 2b(1-76 deleted AGO-binding domain failed to suppress the RDR1/RDR6-dependent degradation of viral RNAs. The mutant CMV2b(8-111 expressing mutant 2b, in which the N-terminal 7 amino acid (aa was deleted, exhibited slightly reduced virulence, but not viral RNA levels, in both wild-type and rdr1/6 plants, which indicated that 2b retained the AGO-binding activity acquired the counter-RDRs degradation of viral RNAs. The deletion of the N-terminal 7 aa of 2b affected virulence due to the reduced affinity for long dsRNA. The mutant CMV2b(18-111 expressing mutant 2b lacked the N-terminal 17 aa but retained its AGO-binding activity greatly reduced virulence and viral RNA level. Together with the instability of both 2b(18-111-EGFP and RFP-AGO4 proteins when co-expressed in Nicotiana benthamiana leaves, our data demonstrates that the effect of 2b-AGO interaction on counter-RDRs antiviral defense required the presence of 2b dsRNA-binding activity. Taken together, our findings demonstrate that the dsRNA-binding activity of the

  20. Zebrafish stem/progenitor factor msi2b exhibits two phases of activity mediated by different splice variants.

    Science.gov (United States)

    Hochgreb-Hägele, Tatiana; Koo, Daniel E S; Das, Neha M; Bronner, Marianne E

    2014-02-01

    The Musashi (Msi) family of RNA-binding proteins is important in stem and differentiating cells in many species. Here, we present a zebrafish gene/protein trap line gt(msi2b-citrine)(ct) (57) (a) that expresses a Citrine fusion protein with endogenous Msi2b. Our results reveal two phases of Msi2b expression: ubiquitous expression in progenitor cells in the early embryo and later, tissue-specific expression in differentiating cells in the olfactory organ, pineal gland, and subpopulations of neurons in the central nervous system (CNS). Interestingly, this division between early and late phases is paralleled by differential expression of msi2b alternative splicing products. Whereas the full-length and long variant v3 Msi2b predominate at early stages, the later expression of variants in differentiating tissues appears to be tissue specific. Using the gt(msi2b-citrine)(ct) (57) (a), we characterized tissue-specific expression of Msi2b with cellular resolution in subsets of differentiating cells in the olfactory organ, pineal gland, CNS, and ventral neural tube. By performing transcription activator-like effectors nuclease-mediated biallelic genome editing or morpholino knockdown of Msi2b in zebrafish, our results show that early inactivation of Msi2b results in severe embryonic defects including hypertrophy of the ventricles and shortening of the body, consistent with an important role in cell proliferation and survival. Moreover, specific inactivation of Msi2b full-length indicates that this species is essential for the early role of Msi2b. This line provides a valuable tool both for live imaging of the endogenous Msi2b at subcellular resolution and manipulation of Msi2b-expressing cells.

  1. Populating the i2b2 database with heterogeneous EMR data: a semantic network approach.

    Science.gov (United States)

    Mate, Sebastian; Bürkle, Thomas; Köpcke, Felix; Breil, Bernhard; Wullich, Bernd; Dugas, Martin; Prokosch, Hans-Ulrich; Ganslandt, Thomas

    2011-01-01

    In an ongoing effort to share heterogeneous electronic medical record (EMR) data in an i2b2 instance between the University Hospitals Münster and Erlangen for joint cancer research projects, an ontology based system for the mapping of EMR data to a set of common data elements has been developed. The system translates the mappings into local SQL scripts, which are then used to extract, transform and load the facts data from each EMR into the i2b2 database. By using Semantic Web standards, it is the authors' goal to reuse the laboriously compiled "mapping knowledge" in future projects, such as a comprehensive cancer ontology or even a hospital-wide clinical ontology.

  2. Characteristics of the brand building on the business (B2B market

    Directory of Open Access Journals (Sweden)

    Gligorijević Mirjana

    2011-01-01

    Full Text Available This paper analyzes the characteristics of the brand building in the business (B2B market. Branding strategy at the business market is complex and difficult to implement because of the many limiting factors. Building a brand in the business market is marked by very specific characteristics of industrial products. The value of B2B brands is built through functional characteristics and performances of the product (functional values and emotional value, which together guarantee the delivery a unique experience of business customers. All marketing mix tools can be considered to be branding instruments. The purpose of this paper is to emphasize the importance of applying a branding strategy on business market.

  3. The role of orbiting resonances in the vibrational predissociation of Ne-Br{sub 2}(B)

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Vela, A [Instituto de Fisica Fundamental, CSIC, Serrano 123, 28006 Madrid (Spain)], E-mail: garciavela@imaff.cfmac.csic.es

    2009-10-15

    The spectrum of Ne-Br{sub 2}(B,v) orbiting resonances embedded in the continuum of the v=25 vibrational manifold has been studied and compared with the spectrum previously obtained for v=26. The spectra of orbiting resonances are found to be very similar in the two vibrational manifolds, with the resonances located at nearly the same energy positions and with similar widths. The same result was found for the spectra of orbiting resonances of He-I{sub 2}(B,v) for v=59 and 60. This confirms that the nature of the continuum resonances is the same in both van der Waals complexes, and suggests that this type of resonance might be present in other van der Waals rare gas-halogen clusters.

  4. B2B SME Management of Antecedents to the Application of Social Media

    DEFF Research Database (Denmark)

    Brink, Tove

    2017-01-01

    This paper elucidates how business-to-business (B2B) small and medium-sized enterprises (SMEs) can manage antecedents to the application of social media for potential contributions to their business. This in-depth qualitative research study was conducted at four plastic-producing SMEs from October...... 2013 to October 2014, with follow-up interviews in October 2015. The findings reveal two important antecedents to the application of social media that overcome the gap between acknowledging the usefulness of social media and its actual limited application in practical B2B contexts. First, open...... collaborative business model innovation is needed to apply social media in local business processes. Second, central and distributed leadership must be integrated to create ownership and responsibility across the SME organisation and beyond to customers and partners. These findings differ from the social media...

  5. Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes.

    Science.gov (United States)

    El Maatougui, Abdelaziz; Azuaje, Jhonny; González-Gómez, Manuel; Miguez, Gabriel; Crespo, Abel; Carbajales, Carlos; Escalante, Luz; García-Mera, Xerardo; Gutiérrez-de-Terán, Hugo; Sotelo, Eddy

    2016-03-10

    Three novel families of A2B adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin-2(1H)-one chemotype. The most appealing series contain imidazole, 1,2,4-triazole, or benzimidazole rings fused to the 2,3-positions of the parent diazinone core. The optimization process enabled identification of a highly potent (3.49 nM) A2B ligand that exhibits complete selectivity toward A1, A2A, and A3 receptors. The results of functional cAMP experiments confirmed the antagonistic behavior of representative ligands. The main SAR trends identified within the series were substantiated by a molecular modeling study based on a receptor-driven docking model constructed on the basis of the crystal structure of the human A2A receptor.

  6. Histone H2A and H2B Deubiquitinase in Developmental Disease and Cancer

    Directory of Open Access Journals (Sweden)

    Demeng Chen

    2015-01-01

    Full Text Available Histone H2A and H2B ubiquitination represents a widely used mechanism for a variety of regulatory transcriptional programs. In this review, structural and functional studies of histone H2A and histone H2B deubiquitinase (DUB, DUB including 2A-DUB, BRCA1-associated protein-1, USP3, UBP8, and USP16, and their role in developmental disease and carcinogenesis were recapitulated. Also the progress in developing small molecular inhibitors targeting DUBs and their application in colon cancer, B-cell lymphoma, and multiple myeloma were summarized. Overall, the study seek to strengthen the understanding on how these DUBs contribute to normal and malignant tissue development thus aiding in improving the design of therapeutic strategies used for diagnosis and prognosis of the disease.

  7. Unique features of monoclonal IgG2b in the cleavage reaction with pepsin.

    Directory of Open Access Journals (Sweden)

    Sumii,Hiroshi

    1989-06-01

    Full Text Available Preparations of IgG2b purified from several mouse hybridoma clones were highly susceptible, compared to other subclasses, to peptic digestion under conditions usually used to prepare F (ab'2 fragments. Analyses of the digestion products revealed that no F (ab'2 was produced and that the main product was a Fab-like fragment. Demonstration of the hinge disulfides in the Fc portion clearly indicated that in IgG2b the primary peptic cleavage occurs on the NH2-terminal side of the inter-heavy chain disulfide bridge. The resulting Fab failed to bind with antigen, suggesting the importance of the CH1-hinge region in maintaining the native conformation of the antigen-binding site.

  8. Genetic characterization of a noncytopathic bovine viral diarrhea virus 2b isolated from cattle in China.

    Science.gov (United States)

    Wang, Wei; Shi, Xinchuan; Chen, Chaoyang; Wu, Hua

    2014-10-01

    In January 2013, several clinical signs of cattle with diarrhea, cough, nasal discharge, and fever were reported in Jilin province, China. One virus named SD1301 was isolated and identified. Complete genome of the virus is 12258nt in length and contains a 5'UTR, one open reading frame encoding a polyprotein of 3,897 amino acids and a 3'UTR. Phylogenetic analysis of 5'UTR, N(pro), E1 and E2 gene demonstrated the virus belonged to BVDV 2b, and genetically related to the BVDV strain Hokudai-Lab/09 from Japan in 2010. This bovine viral diarrhea virus displays a unique genetic signature with 27-nucleotide deletion in the 5'UTR, which is similar to the bovine viral diarrhea virus C413 (AF002227). This was the first confirmed isolation of ncp BVDV2b circulating in bovine herd of China.

  9. Ground-based Multi-object Spectroscopy of XO-2b using a Systematic Wavelength Calibration

    Science.gov (United States)

    Pearson, Kyle; Griffith, Caitlin Ann; Zellem, Robert Thomas

    2016-10-01

    Here we present multiple observations of the primary transit of the bright hot-Jupiter XO-2b with visible wavelength spectroscopy. Repeated observations of XO-2b record simulatenous measurements of both the exoplanet host star and one or more comparison stars. Ideally, the comparison star measures errors, such as airmass variations and telescope jitter. The hypothesis is that these errors can then be divided out from the target star to achieve higher SNR and improve estimation of the small transit signal. However, we find that the astrophysical signals are subject to time-varying translations along the spectroscopic dispersion axis that change according to wavelength. Improper alignment prior to dividing the astrophysical signals can result in spurious spectral features or inadequate removal of shared systematics. We showcase ways to check for inadequate alignment and offer corrections to such problems.

  10. An i2b2-based, generalizable, open source, self-scaling chronic disease registry

    OpenAIRE

    Natter, Marc D; Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E.; Wallace, Carol A.; Warren, Robert W.; Weber, Griffin M.; Mandl, Kenneth D

    2013-01-01

    Objective Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health...

  11. An i2b2-based, generalizable, open source, self-scaling chronic disease registry

    OpenAIRE

    Natter, Marc D; Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E.; Wallace, Carol A.; Warren, Robert W.; Weber, Griffin M.; Mandl, Kenneth D

    2012-01-01

    Objective: Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Healt...

  12. Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development.

    Science.gov (United States)

    Teslaa, Jessica J; Keller, Abigail N; Nyholm, Molly K; Grinblat, Yevgenya

    2013-08-01

    Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) neural crest induction and migration, and (2) early

  13. The FRCR 2B examination: a survey of candidate perceptions and experiences

    Energy Technology Data Exchange (ETDEWEB)

    Yeung, A., E-mail: andrewyeung@hotmail.co [Department of Radiology, Freeman Hospital, Newcastle upon Tyne (United Kingdom); Booth, T.C. [Department of Radiology, Royal Free Hospital, London (United Kingdom); Jacob, K. [Department of Radiology, Weston General Hospital, Weston-super-Mare (United Kingdom); McCoubrie, P. [Department of Radiology, Southmead Hospital, Bristol (United Kingdom); McKnight, L. [Department of Radiology, Morriston Hospital, Swansea (United Kingdom)

    2011-05-15

    Aim: To survey the views of recent candidates of the Fellowship of the Royal College of Radiologists (FRCR) 2B examination with reference to assessment validity, reliability, and acceptability. Materials and methods: One thousand, two hundred and four UK radiology trainees and consultants were invited to complete an automated internet questionnaire regarding their experiences and perceptions of the FRCR 2B examination. The questionnaire was informed by a review of the literature. Eligible participants were candidates who had taken the examination within the previous 3 years. Results: Four hundred and ninety-seven out of 1204 (41%) responses were received; of which 258/497 (52% of respondents) were eligible for inclusion into the study. The rapid reporting component is perceived to be significantly fairer than the oral section (82 versus 70% agree; p < 0.001). The oral component fared poorly in perceived performance-reducing anxiety levels but well in questions relating to validity and reliability. Female candidates are more likely to find the FRCR 2B unfair (p = 0.01) and experience performance-reducing anxiety (p < 0.001) than males. No gender differences were observed in first-time pass rates (p = 0.6). Candidate first language did not affect anxiety levels (p = 0.9) or first-time pass rates (p = 0.06). Only 12% of candidates agreed that the oral examination should move to an objective structured clinical format. Conclusion: Candidates score the FRCR 2B examination well in test validity with little desire for change to the oral examination format. Efforts to help reduce anxiety levels in the oral component would improve perceived fairness.

  14. Effect of the Ni site substitution on superconducting properties of YNi 2B 2C

    Science.gov (United States)

    Bud'ko, S. L.; Elmassalami, M.; Fontes, M. B.; Mondragon, J.; Vanoni, W.; Giordanengo, B.; Baggio-Saitovitch, E. M.

    1995-02-01

    Structural and superconducting properties of Y(Ni 1- xM x) 2B 2C compounds with MCo, Fe and Ru have been studied. A fast decrease of Tc with the concentration of the dopants was found. This effect can be attributed to the shift of the Fermi level induced by the dopant concentration with the additional contributions from the chemical-pressure effects and from the decrease of the electronic mean free path.

  15. Granulin exacerbates lupus nephritis via enhancing macrophage M2b polarization.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available BACKGROUND AND AIMS: Lupus nephritis (LN, with considerable morbidity and mortality, is one of the most severe manifestations of systemic lupus erythematosus (SLE. Yet, the pathogenic mechanisms of LN have not been clearly elucidated, and efficient therapies are still in great need. Granulin (GRN, a multifunctional protein linked to inflammatory diseases, has recently been reported to correlate with the disease activity of autoimmune diseases. However, the role of GRN in the pathogenic process of LN still remains obscure. In this study, we explored its potential role and underlying mechanism in the pathogenesis of LN. METHODOLOGY/PRINCIPAL FINDINGS: We found that serum GRN levels were significantly up-regulated and were positively correlated with the severity of LN. Overexpression of GRN in vivo by transgenic injection remarkably exacerbated LN, whereas down-regulation of GRN with shRNA ameliorated LN, firmly demonstrating the critical role of GRN in the pathogenesis of LN. Notably, macrophage phenotype analysis revealed that overexpression of GRN could enhance macrophage polarization to M2b, a key mediator of the initiation and progression of LN. On the contrary, down-regulation of GRN resulted in impaired M2b differentiation, thus ameliorating LN. Moreover, we found that MAPK signals were necessary for the effect of GRN on macrophage M2b polarization. CONCLUSION/SIGNIFICANCE: We first demonstrated that GRN could aggravate lupus nephritis (LN via promoting macrophage M2b polarization, which might provide insights into the pathogenesis of LN as well as potential therapeutic strategies against LN.

  16. B2B Strategy Making and Planning : case: Datnam Techonologies and Trading Company, Ltd.

    OpenAIRE

    Hoang, Hong Tu

    2013-01-01

    There is an increasing demand for safety and security equipment market in Vietnam thanks to the encouragement of the government and the growing concentration on working condition improvement. Therefore the Case Company Datnam Technology and Trading Company, Ltd., a successful SME in Vietnam, realized the rising demand in business to business (B2B) market and assigned the author to do research about this topic. The purpose of the study is to assist the company to launch the Breath Alcohol T...

  17. Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Wolfgang Blenau

    2017-05-01

    Full Text Available Serotonin (5-hydroxytryptamine, 5-HT is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects and deuterostomes (e.g., mammals. In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster, a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT1A, Dm5-HT1B, and Dm5-HT7 couple to cAMP signaling cascades, the Dm5-HT2A receptor leads to Ca2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT2B receptor. Knowledge about this receptor’s pharmacological properties is very limited. This is quite surprising because Dm5-HT2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT2B’s pharmacology, we evaluated the receptor’s response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT2B signaling in vitro and in vivo.

  18. Interdependence of magnetism and superconductivity in the borocarbide TmNi2B2C

    DEFF Research Database (Denmark)

    Nørgaard, K.; Eskildsen, M.R.; Andersen, N.H.

    2000-01-01

    We have discovered anew antiferromagnetic phase in TmNi2B2C by neutron diffraction. The ordering vector is Q(A) = (0.48,0,0) and the phase appears shove a critical in-plans magnetic field of 0.9 T. The field was applied in order to test the assumption that the zero-field magnetic structure at Q...

  19. Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2.

    Science.gov (United States)

    Chen, W; Kowatch, R; Lin, S; Splaingard, M; Huang, Y

    2015-01-01

    Nationwide Children's Hospital established an i2b2 (Informatics for Integrating Biology & the Bedside) application for sleep disorder cohort identification. Discrete data were gleaned from semistructured sleep study reports. The system showed to work more efficiently than the traditional manual chart review method, and it also enabled searching capabilities that were previously not possible. We report on the development and implementation of the sleep disorder i2b2 cohort identification system using natural language processing of semi-structured documents. We developed a natural language processing approach to automatically parse concepts and their values from semi-structured sleep study documents. Two parsers were developed: a regular expression parser for extracting numeric concepts and a NLP based tree parser for extracting textual concepts. Concepts were further organized into i2b2 ontologies based on document structures and in-domain knowledge. 26,550 concepts were extracted with 99% being textual concepts. 1.01 million facts were extracted from sleep study documents such as demographic information, sleep study lab results, medications, procedures, diagnoses, among others. The average accuracy of terminology parsing was over 83% when comparing against those by experts. The system is capable of capturing both standard and non-standard terminologies. The time for cohort identification has been reduced significantly from a few weeks to a few seconds. Natural language processing was shown to be powerful for quickly converting large amount of semi-structured or unstructured clinical data into discrete concepts, which in combination of intuitive domain specific ontologies, allows fast and effective interactive cohort identification through the i2b2 platform for research and clinical use.

  20. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  1. Inositol hexakisphosphate suppresses excitatory neurotransmission via synaptotagmin-1 C2B domain in the hippocampal neuron

    Science.gov (United States)

    Yang, Shao-Nian; Shi, Yue; Yang, Guang; Li, Yuxin; Yu, Lina; Shin, Ok-Ho; Bacaj, Taulant; Südhof, Thomas C.; Yu, Jia; Berggren, Per-Olof

    2012-01-01

    Inositol hexakisphosphate (InsP6) levels rise and fall with neuronal excitation and silence, respectively, in the hippocampus, suggesting potential signaling functions of this inositol polyphosphate in hippocampal neurons. We now demonstrate that intracellular application of InsP6 caused a concentration-dependent inhibition of autaptic excitatory postsynaptic currents (EPSCs) in cultured hippocampal neurons. The treatment did not alter the size and replenishment rate of the readily releasable pool in autaptic neurons. Intracellular exposure to InsP6 did not affect spontaneous EPSCs or excitatory amino acid-activated currents in neurons lacking autapses. The InsP6-induced inhibition of autaptic EPSCs was effectively abolished by coapplication of an antibody to synaptotagmin-1 C2B domain. Importantly, preabsorption of the antibody with a GST-WT synaptotagmin-1 C2B domain fragment but not with a GST-mutant synaptotagmin-1 C2B domain fragment that poorly reacted with the antibody impaired the activity of the antibody on the InsP6-induced inhibition of autaptic EPSCs. Furthermore, K+ depolarization significantly elevated endogenous levels of InsP6 and occluded the inhibition of autaptic EPSCs by exogenous InsP6. These data reveal that InsP6 suppresses excitatory neurotransmission via inhibition of the presynaptic synaptotagmin-1 C2B domain-mediated fusion via an interaction with the synaptotagmin Ca2+-binding sites rather than via interference with presynaptic Ca2+ levels, synaptic vesicle trafficking, or inactivation of postsynaptic ionotropic glutamate receptors. Therefore, elevated InsP6 in activated neurons serves as a unique negative feedback signal to control hippocampal excitatory neurotransmission. PMID:22778403

  2. A New Sesquiterpene from Caragana intermediia and Its Anti-Pyricularia oryzae P-2b Activity

    Institute of Scientific and Technical Information of China (English)

    SUN Zhi-Hua; HU Chang-Qi; WANG Jin-Yi

    2008-01-01

    A new aromadendrane-type sesquiterpene,(-)-alloaromadendrane-4β,10β-diol(1),has been isolated from the aerial part of Caragana intermediia,the structure of which was established by spectroscopic methods,including X-ray analysis that provided its relative stereochemistry.Bioassay showed that 1 possessed anti-Pyricularia oryzae P-2b activity with an MIC(minimum inhibitory concentration)value of 10μg/mL.

  3. Filter Bank Common Spatial Pattern algorithm on BCI Competition IV Datasets 2a and 2b

    Directory of Open Access Journals (Sweden)

    Kai Keng eAng

    2012-03-01

    Full Text Available The Common Spatial Pattern (CSP algorithm is an effective and popular method for classifying 2-class motor imagery electroencephalogram (EEG data, but its effectiveness depends on the subject-specific frequency band. This paper presents the Filter Bank Common Spatial Pattern (FBCSP algorithm to optimize the subject-specific frequency band for CSP on Datasets 2a and 2b of the Brain-Computer Interface (BCI Competition IV. Dataset 2a comprised 4 classes of 22 channels EEG data from 9 subjects, and Dataset 2b comprised 2 classes of 3 bipolar channels EEG data from 9 subjects. Multi-class extensions to FBCSP are also presented to handle the 4-class EEG data in Dataset 2a, namely, Divide-and-Conquer (DC, Pair-Wise (PW, and One-Versus-Rest (OVR approaches. Two feature selection algorithms are also presented to select discriminative CSP features on Dataset 2b, namely, the Mutual Information-based Best Individual Feature (MIBIF algorithm, and the Mutual Information-based Rough Set Reduction (MIRSR algorithm. The single-trial classification accuracies were presented using 10x10-fold cross-validations on the training data and session-to-session transfer on the evaluation data from both datasets. Disclosure of the test data labels after the BCI Competition IV showed that the FBCSP algorithm performed relatively the best among the other submitted algorithms and yielded a mean kappa value of 0.569 and 0.600 across all subjects in Datasets 2a and 2b respectively.

  4. Filter Bank Common Spatial Pattern Algorithm on BCI Competition IV Datasets 2a and 2b.

    Science.gov (United States)

    Ang, Kai Keng; Chin, Zheng Yang; Wang, Chuanchu; Guan, Cuntai; Zhang, Haihong

    2012-01-01

    The Common Spatial Pattern (CSP) algorithm is an effective and popular method for classifying 2-class motor imagery electroencephalogram (EEG) data, but its effectiveness depends on the subject-specific frequency band. This paper presents the Filter Bank Common Spatial Pattern (FBCSP) algorithm to optimize the subject-specific frequency band for CSP on Datasets 2a and 2b of the Brain-Computer Interface (BCI) Competition IV. Dataset 2a comprised 4 classes of 22 channels EEG data from 9 subjects, and Dataset 2b comprised 2 classes of 3 bipolar channels EEG data from 9 subjects. Multi-class extensions to FBCSP are also presented to handle the 4-class EEG data in Dataset 2a, namely, Divide-and-Conquer (DC), Pair-Wise (PW), and One-Versus-Rest (OVR) approaches. Two feature selection algorithms are also presented to select discriminative CSP features on Dataset 2b, namely, the Mutual Information-based Best Individual Feature (MIBIF) algorithm, and the Mutual Information-based Rough Set Reduction (MIRSR) algorithm. The single-trial classification accuracies were presented using 10 × 10-fold cross-validations on the training data and session-to-session transfer on the evaluation data from both datasets. Disclosure of the test data labels after the BCI Competition IV showed that the FBCSP algorithm performed relatively the best among the other submitted algorithms and yielded a mean kappa value of 0.569 and 0.600 across all subjects in Datasets 2a and 2b respectively.

  5. Homology modeling of NR2B modulatory domain of NMDA receptor and analysis of ifenprodil binding.

    Science.gov (United States)

    Marinelli, Luciana; Cosconati, Sandro; Steinbrecher, Thomas; Limongelli, Vittorio; Bertamino, Alessia; Novellino, Ettore; Case, David A

    2007-10-01

    NMDA receptors are glutamate-gated ion channels (iGluRs) that are involved in several important physiological functions such as neuronal development, synaptic plasticity, learning, and memory. Among iGluRs, NMDA receptors have been perhaps the most actively investigated for their role in chronic neurodegeneration such as Alzheimer's, Parkinson's, and Huntington's diseases. Recent studies have shown that the NTD of subunit NR2B modulates ion channel gating through the binding of allosteric modulators such as the prototypical compound ifenprodil. In the present paper, the construction of a three-dimensional model for the NR2B modulatory domain is described and docking calculations allow, for the first time, definition of the ifenprodil binding pose at an atomic level and fully explain all the available structure-activity relationships. Moreover, in an attempt to add further insight into the ifenprodil mechanism of action, as it is not completely clear if it binds and stabilizes an open or a closed conformation of the NR2B modulatory domain, a matter, which is fundamental for the rational design of NMDA antagonists, MD simulations followed by an MM-PBSA analysis were performed. These calculations reveal that the closed conformation of the R1-R2 domain, rather than the open, constitutes the high affinity binding site for ifenprodil and that a profound stabilization of the closed conformation upon ifenprodil binding occurs. Thus, for a rational design and/or for virtual screening experiments, the closed conformation of the R1-R2 domain should be taken into account and our 3D model can provide valuable hints for the design of NR2B-selective antagonists.

  6. Prevention of Adenovirus Infection with Recombinant Interferon 2b Medication in Preschool Institutions

    Directory of Open Access Journals (Sweden)

    L. V. Osidak

    2016-01-01

    Full Text Available This article presents the results of experimental (on cell cultures and clinical (in children’s groups studies of recombinant interferon alpha-2b medication (Grippferon. Our aim was to examine the virus-inhibitory activity of this medication (against adenovirus and its preventive effect (on causative agents of ARVI, which allows us to use this medication as a preventive measure against adenovirus (as well as any other infection in children’s groups.

  7. Inactivated chimeric porcine circovirus (PCV) 1-2 vaccines based on genotypes 2b and 2d exhibit similar immunological effectiveness in protecting pigs against challenge with PCV2b strain 0233.

    Science.gov (United States)

    Li, Jizong; Yu, Tianqi; Zhang, Feipeng; Wang, Xiaobo; Zhou, Jinzhu; Gao, Xing; Gao, Song; Liu, Xiufan

    2017-01-01

    Porcine circovirus type 2 (PCV2) is subdivided into four genotypes: PCV2a, PCV2b, PCV2c and PCV2d. Here, for the first time, we compared the efficacy of two experimental inactivated chimeric PCV1-2 vaccines based on genotypes 2b and 2d. Seventeen 3-week-old pigs were divided randomly into four groups. Group 1 and 2 pigs were inoculated with genotype 2b- and 2d-based inactivated vaccines, respectively. At 28 days post-vaccination (DPV), pigs in groups 1-3 were challenged with the PCV2b 0233 strain. All experimental pigs were necropsied at 21 days post-challenge (DPC). Pigs vaccinated with the genotype 2b- or 2d-based vaccine had high antibody titres and lower PCV2b copy numbers in samples of sera, faeces and nasal secretions compared with pigs in the unvaccinated challenge group. Interestingly, we detected no DNA from the challenge strain in the superficial inguinal lymph nodes of the pigs immunized with the PCV2b vaccine, while one pig in the PCV2d- immunized group had detectable DNA from the challenge strain at 21 DPC. We found no significant differences in the humoral immune response, PCV2b load, or PCV-related microscopic lesions between the two vaccinated groups post-challenge. Therefore, both vaccines were equally effective at inducing immunity against challenge with PCV2b strain 0233.

  8. What Caused the Lead burn-out in Spectrometer Magnet 2B

    Energy Technology Data Exchange (ETDEWEB)

    Green, Michael A

    2010-11-29

    The spectrometer solenoids are supposed to be the first magnets installed in the MICE Cooling Channel. The results of the test of Spectrometer Magnet 2B are reported in a previous MICE Note. Magnet 2B was tested with all five coils connected in series. The magnet failed because a lead to coil M2 failed before it could be trained to its full design current of 275 A. First, this report describes the condition of the magnet when the lead failure occurred. The lead that failed was between the cold mass feed-through and the heavy lead that connected to coil M2 and the quench protection diodes. It is believed that the lead failed because the minimum propagation zone (MPZ) length was too short. The quench was probably triggered by lead motion in the field external to the magnet center coil. The effect of heat transfer on quench propagation and MPZ length is discussed. The MPZ length is compared for a number of cases that apply to the spectrometer solenoid 2B as built and as it has been repaired. The required heat transfer coefficient for cryogenic stability and the quench propagation velocity along the leads are compared for various parts of the Magnet leads inside the cold mass cryostat. The effect of the insulation on leads on heat transfer is and stability is discussed.

  9. Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China.

    Directory of Open Access Journals (Sweden)

    Zhen Zhu

    Full Text Available A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.

  10. Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China.

    Science.gov (United States)

    Zhu, Zhen; Pan, Guixia; Zhou, Shujie; Dai, Jingjing; Chen, Xia; Tang, Jihai; Chen, Shuping; Zheng, Yilun; Song, Jie; Xu, Wenbo

    2015-01-01

    A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV) was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.

  11. Information management: The adoption of order processing for B2B e-commerce

    Directory of Open Access Journals (Sweden)

    F. W. Voges

    2007-11-01

    Full Text Available The management of information flow in the order processing activities of small enterprises is not always understood. An inefficient supply chain is often the result of the lack of timely and accessible inter-firm information and data exchange. Small suppliers often do not have the technology infrastructure and capable resources available for proper integration with supply chains. This research investigated suppliers and fast moving consumer goods (FMCG retailers, adopting business-to-business (B2B e-commerce. Small businesses are the focus of this research, as they contribute to a large portion of the South African economy and play an important role in the supply chains of retailers. Case study research using evidence obtained from nine small, medium and micro enterprises (SMMEs and suppliers located in the Western Cape, South Africa, was used. It was found that small suppliers have different processes for conducting business with various retailers. Literature revealed little evidence of using the Internet as an enabling technology in on-line order processing. From the analysis, nine improvement areas were identified to enhance the conduct of efficient B2B order processing and associated information flow. These improvement areas were merged with four factors that were identified in a framework when adopting e-supply chains. This resulted in the proposition of guidelines for small suppliers when adopting B2B e-commerce for order processing.

  12. Intensive Farmaco- Surveillance of Interferon Alpha 2b Recombinant in Multiple Sclerosis.

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    Leslie Pérez Ruiz

    2007-12-01

    Full Text Available Background: The interferon alpha 2b recombinant, produced in Cuba, is used in the treatment of different illnesses, such as the multiple sclerosis. For its commercialization it is needed to know its safety scope. Objective: To assess the adverse reactions of interferon alpha 2b recombinant in the treatment of multiple sclerosis. Method: During the period between 1996 and 2006, 70 clinical histories and data collection notebooks of patients included in the randomized double blind national clinical trial phase IV were revised. This trial was developed in the Clinic of Multiple Sclerosis of the Hospital "Dr. Gustavo Aldereguía Lima" in Cienfuegos. With regard to the total of manifested adverse reactions we analyzed type, length, and use of a given treatment to counteract them, intensity level (light, moderate, serious or lethal and causality level (definitive, probable, possible, conditional or not related. Results: 53 patients out of the total presented 207 adverse reactions to interferon. The most frequent were: fever, migraine, chills, arthralgia, asthenia and myalgia, being most of them moderate collateral effects of definitive character. In 197 patients the outcome was favorable. Conclusion: The use of the interferon alpha 2b recombinant was safe in the treatment of the multiple sclerosis in these patients. 

  13. HATS-2b: A transiting extrasolar planet orbiting a K-type star showing starspot activity

    CERN Document Server

    Mohler-Fischer, M; Hartman, J D; Bakos, G B; Penev, K; Bayliss, D; Jordan, A; Csubry, Z; Zhou, G; Rabus, M; Nikolov, N; Brahm, R; Espinoza, N; Buchhave, L A; Beky, B; Suc, V; Csak, B; Henning, T; Wright, D J; Tinney, C G; Addison, B C; Schmidt, B; Noyes, R W; Papp, I; Lazar, J; Sari, P; Conroy, P

    2013-01-01

    We report the discovery of HATS-2b, the second transiting extrasolar planet detected by the HATSouth survey. HATS-2b is moving on a circular orbit around a V=13.6 mag, K-type dwarf star (GSC 6665-00236), at a separation of 0.0230 \\pm 0.0003 AU and with a period of 1.3541 days. The planetary parameters have been robustly determined using a simultaneous fit of the HATSouth, MPG/ESO~2.2\\,m/GROND, Faulkes Telescope South/Spectral transit photometry and MPG/ESO~2.2\\,m/FEROS, Euler~1.2\\,m/CORALIE, AAT~3.9\\,m/CYCLOPS radial-velocity measurements. HATS-2b has a mass of 1.37 \\pm 0.16 M_J, a radius of 1.14 \\pm 0.03 R_J and an equilibrium temperature of 1567 \\pm 30 K. The host star has a mass of 0.88 \\pm 0.04 M_Sun, radius of 0.89 \\pm 0.02 R_Sun and shows starspot activity. We characterized the stellar activity by analysing two photometric follow-up transit light curves taken with the GROND instrument, both obtained simultaneously in four optical bands (covering the wavelength range of 3860-9520 \\AA). The two light curv...

  14. Pre-Launch Absolute Calibration of CCD/CBERS-2B Sensor

    Science.gov (United States)

    Ponzoni, Flávio Jorge; Albuquerque, Bráulio Fonseca Carneiro

    2008-01-01

    Pre-launch absolute calibration coefficients for the CCD/CBERS-2B sensor have been calculated from radiometric measurements performed in a satellite integration and test hall in the Chinese Academy of Space Technology (CAST) headquarters, located in Beijing, China. An illuminated integrating sphere was positioned in the test hall facilities to allow the CCD/CBERS-2B imagery of the entire sphere aperture. Calibration images were recorded and a relative calibration procedure adopted exclusively in Brazil was applied to equalize the detectors responses. Averages of digital numbers (DN) from these images were determined and correlated to their respective radiance levels in order to calculate the absolute calibration coefficients. It has been the first time these pre-launch absolute calibration coefficients have been calculated considering the Brazilian image processing criteria. Now it will be possible to compare them to those that will be calculated from vicarious calibration campaigns. This comparison will permit the CCD/CBERS-2B monitoring and the frequently data updating to the user community. PMID:27873886

  15. Atmospheric Circulation of Eccentric Hot Jupiter HAT-P-2b

    CERN Document Server

    Lewis, Nikole K; Fortney, Jonathan J; Knutson, Heather A; Marley, Mark S

    2014-01-01

    The hot-Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse even...

  16. PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models

    Science.gov (United States)

    Sabha, Nesrin; Volpatti, Jonathan R.; Gonorazky, Hernan; Davidson, Ann E.; Li, Xingli; Eltayeb, Nadine M.; Dall’Armi, Claudia; Di Paolo, Gilbert; Brooks, Susan V.; Buj-Bello, Ana; Feldman, Eva L.; Dowling, James J.

    2016-01-01

    Myotubular myopathy (MTM) is a devastating pediatric neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments. We have previously shown phosphatidylinositol-3-phosphate (PI3P) accumulation in animal models of MTM. Here, we tested the hypothesis that lowering PI3P levels may prevent or reverse the MTM disease process. To test this, we targeted class II and III PI3 kinases (PI3Ks) in an MTM1-deficient mouse model. Muscle-specific ablation of Pik3c2b, but not Pik3c3, resulted in complete prevention of the MTM phenotype, and postsymptomatic targeting promoted a striking rescue of disease. We confirmed this genetic interaction in zebrafish, and additionally showed that certain PI3K inhibitors prevented development of the zebrafish mtm phenotype. Finally, the PI3K inhibitor wortmannin improved motor function and prolonged lifespan of the Mtm1-deficient mice. In all, we have identified Pik3c2b as a genetic modifier of Mtm1 mutation and demonstrated that PIK3C2B inhibition is a potential treatment strategy for MTM. In addition, we set the groundwork for similar reciprocal inhibition approaches for treating other PIP metabolic disorders and highlight the importance of modifier gene pathways as therapeutic targets. PMID:27548528

  17. Li2B3O4F3, a new lithium-rich fluorooxoborate

    Science.gov (United States)

    Pilz, Thomas; Nuss, Hanne; Jansen, Martin

    2012-02-01

    The new lithium fluorooxoborate, Li2B3O4F3, is obtained by a solid state reaction from LiBO2 and LiBF4 at 553 K and crystallizes in the acentric orthorhombic space group P212121 (no. 19) with the cell parameters a=4.8915(9), b=8.734(2), and c=12.301(2) Å. Chains of fluorinated boroxine rings along the b axis consists of BO3 triangles and BO2F2 as well as BO3F tetrahedra. Mobile lithium ions are compensating the negative charge of the anionic chain, in which the fourfold coordinated boron atoms bear a negative formal charge. Annealing Li2B3O4F3 at temperatures above 573 K leads to conversion into Li2B6O9F2. The title compound is an ionic conductor with the highest ion conductivity among the hitherto know lithium fluorooxoborates, with conductivities of 1.6×10-9 and 1.8×10-8 S cm-1 at 473 and 523 K, respectively.

  18. The effects of pegylated interferon--alpha2B on mumps orchitis.

    Science.gov (United States)

    Pal, Goutam

    2013-09-01

    To evaluate the effects of pegylated Interferon--alpha2B on mumps orchitis, 80 patients suffering from mumps orchitis, were randomly assigned into 2 groups of 40 patients each. In the first group patients received pegylated interferon--alpha2B and the other group did not, acting as controls. All were confirmed by mumps IgM (ELISA) and evaluated by testis size, semen analysis and hormone level. In the first group, the symptoms resolved within average 2.2 days and testicular size returned to normal within average 5.3 days but in 2nd group, those returned to normal within average 5.7 days and 10.2 days respectively. In the 1st group, oligospermia was detected in 11 patients and subsequently returned to normal in all patients and there was no testicular atrophy. In the 2nd group oligospermia was detected in 13 patients and were persistently low in 3 patients and testicular atrophy detected in 2 patients. The results indicated the beneficial role of pegylated interferon--alpha2B in preventing infertility from mumps orchitis.

  19. CONSTRUCTION AND STUDY OF Althaea officinalis TRANSGENIC ROOTS CULTURE WITH HUMAN INTERFERON α2B GENE

    Directory of Open Access Journals (Sweden)

    N. A. Matvieieva

    2013-04-01

    Full Text Available The aim of our work was to obtain Althaea officinalis L. «hairy» root culture with human interferon α2b gene (ifn-α2b, to measure fructans content and antiviral activity of extracts from the transgenic roots. Transformation of leaf and root explants was carried out by means of Agrobacterium rhizogenes-mediated transformation. Antiviral activity was measured by the reduction in cytopathic effect of vesicular stomatitis virus (Indiana strain in bovine kidney cells line MDBK. Transformation frequency was 100% for leaf and root explants. RT-PCR confirmed ifn- α2b gene transcription. The clones of transgenic roots differed in mass increasing from 0, 036 ± 0,008 up to 0,371 ± 0,019 g in 30 days cultivation and in fructan synthesis from 67,2± 4,47 up to 154,6 ± 6,62 mg/g roots dry weight. Extracts from «hairy»roots culture were characterized by high antiviral activity against vesicular stomatitis virus — up to 26 000 IU/ g of roots fresh weight. In some cases the genetic transformation shown to lead increasing the growth rate and increasing the level of fructan synthesis in transgenic A. officinalis roots. Extracts from cultivated in vitro marshmallow transgenic roots were characterized by high level of antiviral activity against vesicular stomatitis virus. Thus, there were obtained transgenic A. officinalis roots, characterized by high growth rate, significant accumulation of fructans and high antiviral activity.

  20. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

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    Eun Ju Oh

    2016-04-01

    Full Text Available BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2 and microphthalmia-associated transcription factor (MITF in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA and cAMP response element-binding protein (CREB activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

  1. Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines.

    Science.gov (United States)

    Mony, Laetitia; Zhu, Shujia; Carvalho, Stéphanie; Paoletti, Pierre

    2011-06-17

    NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands. While much has been learned recently regarding allosteric inhibition of NMDARs, the structural determinants underlying positive allosteric modulation of these receptors remain poorly defined. Here, we show that polyamines, naturally occurring polycations that selectively enhance NMDARs containing the GluN2B subunit, bind at a dimer interface between GluN1 and GluN2B subunit N-terminal domains (NTDs). Polyamines act by shielding negative charges present on GluN1 and GluN2B NTD lower lobes, allowing their close apposition, an effect that in turn prevents NTD clamshell closure. Our work reveals the mechanistic basis for positive allosteric modulation of NMDARs. It provides the first example of an intersubunit binding site in this class of receptors, a discovery that holds promise for future drug interventions.

  2. The CYP2B6*6 allele significantly alters the N-demethylation of ketamine enantiomers in vitro.

    Science.gov (United States)

    Li, Yibai; Coller, Janet K; Hutchinson, Mark R; Klein, Kathrin; Zanger, Ulrich M; Stanley, Nathan J; Abell, Andrew D; Somogyi, Andrew A

    2013-06-01

    Ketamine is primarily metabolized to norketamine by hepatic CYP2B6 and CYP3A4-mediated N-demethylation. However, the relative contribution from each enzyme remains controversial. The CYP2B6*6 allele is associated with reduced enzyme expression and activity that may lead to interindividual variability in ketamine metabolism. We examined the N-demethylation of individual ketamine enantiomers using human liver microsomes (HLMs) genotyped for the CYP2B6*6 allele, insect cell-expressed recombinant CYP2B6 and CYP3A4 enzymes, and COS-1 cell-expressed recombinant CYP2B6.1 and CYP2B6.6 protein variant. Effects of CYP-selective inhibitors on norketamine formation were also determined in HLMs. The two-enzyme Michaelis-Menten model best fitted the HLM kinetic data. The Michaelis-Menten constants (K(m)) for the high-affinity enzyme and the low-affinity enzyme were similar to those for the expressed CYP2B6 and CYP3A4, respectively. The intrinsic clearance for both ketamine enantiomers by the high-affinity enzyme in HLMs with CYP2B6*1/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. The V(max) and K(m) values for CYP2B6.1 were approximately 160 and 70% of those for CYP2B6.6, respectively. N,N'N'-triethylenethiophosphoramide (thioTEPA) (CYP2B6 inhibitor, 25 μM) and the monoclonal antibody against CYP2B6 but not troleandomycin (CYP3A4 inhibitor, 25 μM) or the monoclonal antibody against CYP3A4 inhibited ketamine N-demethylation at clinically relevant concentrations. The degree of inhibition was significantly reduced in HLMs with the CYP2B6*6 allele (gene-dose P < 0.05). These results indicate a major role of CYP2B6 in ketamine N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity.

  3. Behavior of RNAi suppressor protein 2b of Cucumber mosaic virus in planta in presence and absence of virus.

    Science.gov (United States)

    Praveen, Shelly; Mangrauthia, Satendra K; Singh, Priyanka; Mishra, Anil K

    2008-08-01

    The 2b protein encoded by Cucumber mosaic virus (CMV) has been shown as a virus counter defense factor that interferes with the RNAi pathway. The 2b gene from CMV-banana, New Delhi isolate (CMV-NDLS) was amplified from CMV infected cucumber plants to generate the sense and antisense binary vector constructs for 2b expression and repression in planta. Constitutive expression of 2b gene in healthy Nicotiana tabacum caused phenotypic aberrations during somatic embryogenesis, which were not observed when expressed in CMV infected N. tabacum. Further, the established virus population in CMV infected N. tabacum was not affected by constitutive expression and repression of 2b gene. Thus, indicating its role in initiation of gene silencing, at the early stage of viral infection. This is the first demonstration of differential behavior of 2b suppressor protein in host development in the absence and presence of virus.

  4. Enhanced electrochemical performance of orientated VO2(B) raft-like nanobelt arrays through direct lithiation for lithium ion batteries

    Science.gov (United States)

    Liu, Liang; Liu, Qiang; Zhao, Wen; Li, Guochun; Wang, Limei; Shi, Weidong; Chen, Long

    2017-02-01

    Lithiation modification of VO2(B) has been carried out by a facile hydrothermal process, and the compact and locally ordered VO2(B) raft-like nanobelt arrays have been prepared. The synthesis route provides a new approach to elaborate a VO2(B) nanostructure under a mild environment condition. It is found that the growth mechanism of VO2(B) raft-like nanobelt arrays is different from the traditional nucleation-growth process. A novel chemical lithiating-exfoliating-splitting model is proposed. Compared with the bulk counterpart, the lithiated VO2(B) raft-like nanobelt arrays as cathodes exhibit a higher discharge capacity and an enhanced high-rate performance owing to their increased structural anisotropy and decreased polarization. This work indicates that VO2(B) raft-like nanobelt arrays have great potential applications as cathode materials for lithium ion batteries.

  5. Red wine and component flavonoids inhibit UGT2B17 in vitro

    Directory of Open Access Journals (Sweden)

    Jenkinson Carl

    2012-09-01

    Full Text Available Abstract Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analyzed using HPLC; and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8%, the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HPLC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%, caffeic acid (22% and gallic acid (9%; using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 μM despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolizing enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common

  6. The evidence for association of ATP2B2 polymorphisms with autism in Chinese Han population.

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    Wen Yang

    Full Text Available BACKGROUND: Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca(2+ from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. METHODS: We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT program was used to perform association test for SNPs and haplotype analyses. RESULTS: This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013. While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = -2.482, p = 0.013; Z = -2.591, p = 0.0096. Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180-rs3774179 showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = -2.037, p = 0.042; Global p = 0.03. As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = -2.206, p = 0.027; Global p = 0.04, while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032. These results were still significant after using the permutation method to obtain empirical p values. CONCLUSIONS: Our research suggested that ATP2B2

  7. Hydroxysteroid sulfotransferase SULT2B1b promotes hepatocellular carcinoma cells proliferation in vitro and in vivo.

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    Xiaoming Yang

    Full Text Available Hydroxysteroid sulfotransferase 2B1b (SULT2B1b is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.

  8. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Froguel, Philippe; Falchi, Mario [Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom); Bergman, Richard N. [Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States); McTernan, Philip G. [Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom); Hedner, Thomas; Carlsson, Lena M.S. [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Jacobson, Peter, E-mail: peter.jacobson@medfak.gu.se [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  9. New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth.

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    Chien-Hung Shih

    Full Text Available Neurite outgrowth is an essential process for the establishment of the nervous system. Brain-derived neurotrophic factor (BDNF binds to its receptor TrkB and regulates axonal and dendritic morphology of neurons through signal transduction and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular signaling in various physiological processes. The purpose of this study is to investigate the role of SH2B1 in the development of the central nervous system. In this study, we show that knocking down SH2B1 reduces neurite formation of cortical neurons whereas overexpression of SH2B1β promotes the development of hippocampal neurons. We further demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth and signaling using the established PC12 cells stably expressing TrkB, SH2B1β or SH2B1β mutants. Our data indicate that overexpressing SH2B1β enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest that these two pathways are required for SH2B1β-promoted BDNF-induced neurite outgrowth. Moreover, SH2B1β enhances BDNF-stimulated phosphorylation of signal transducer and activator of transcription 3 at serine 727. Finally, our data indicate that the SH2 domain and tyrosine phosphorylation of SH2B1β contribute to BDNF-induced signaling pathways and neurite outgrowth. Taken together, these findings demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth through enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.

  10. Species-specific induction of CYP2B by 2,4,6-tryphenyldioxane-1,3 (TPD).

    Science.gov (United States)

    Pustylnyak, Vladimir; Pivovarova, Elena; Slynko, Nikolai; Gulyaeva, Lyudmila; Lyakhovich, Vyacheslav

    2009-12-16

    The aim of the current study was to investigate the species-specific induction of CYP2B by 2,4,6-tryphenyldioxane-1,3 (TPD) in relation to activation of CAR. 7-Pentoxyresorufin O-dealkylase (PROD) activity, RT-PCR, Western blot, Electrophoretic mobility shift assays (EMSA). Phenobarbital-like inducer administration significantly up-regulated CYP2B activity in rat and mouse liver in a species-specific manner, in contrast to the effects on CYP2B in lungs, kidneys and brains. In parallel, Western blot analysis showed that the species-specific increase of PROD in liver is related to the high content of CYP2B: phenobarbital (PB) and TPD increased CYP2B in rat liver, PB and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) - in mouse liver. The CYP2B protein level was unchanged in the lungs of rats and mice after inducer treatment, whereas it was not detected in the kidney and brain of control and treated animals. The hepatic CYP2B activity in both species paralleled the increase of CYP2B mRNA. A detectable CYP2B mRNA level was measured in the lungs of untreated mice and rats, though it was unchanged during induction. Noninducibility of CYP2B in extrahepatic tissues accompanied an absence of constitutive androstane receptor (CAR) gene expression in these tissues. In liver CYP2B induction paralleled the high level of CAR expression detected by RT-PCR. Moreover, PB, TPD and TCPOBOP treatment stimulated nuclear accumulation of CAR and increased CAR receptor NR1-binding activity in animal liver in a species-specific manner. We have shown that the increased nuclear accumulation and binding activity of CAR are associated with the species-specific up-regulation of CYP2B by TPD in rat liver.

  11. Parallel Functional Activity Profiling Reveals Valvulopathogens Are Potent 5-Hydroxytryptamine2B Receptor Agonists: Implications for Drug Safety Assessment

    OpenAIRE

    Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N; Allen, John A.; Rogan, Sarah C.; Hanson, Bonnie J.; Revankar, Chetana; Robers, Matt; Doucette, Chris; Roth, Bryan L.

    2009-01-01

    Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine2B (5-HT2B) receptor agonists. We have shown that activation of 5-HT2B receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscen...

  12. Histone demethylase JMJD2B is required for tumor cell proliferation and survival and is overexpressed in gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wenjuan; Zhao, Li; Zang, Wen; Liu, Zhifang; Chen, Long; Liu, Tiantian [Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012 (China); Xu, Dawei, E-mail: Dawei.Xu@ki.se [Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012 (China); Department of Medicine, Division of Hematology, Karolinska University Hospital, Solna and Karolinska Institutet, Stockholm (Sweden); Jia, Jihui, E-mail: jiajihui@sdu.edu.cn [Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012 (China)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer JMJD2B is required for cell proliferation and in vivo tumorigenesis. Black-Right-Pointing-Pointer JMJD2B depletion induces apoptosis and/or cell cycle arrest. Black-Right-Pointing-Pointer JMJD2B depletion activates DNA damage response and enhances p53 stabilization. Black-Right-Pointing-Pointer JMJD2B is overexpressed in human primary gastric cancer. -- Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Jumonji domain containing 2B (JMJD2B) is a newly identified histone demethylase that regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 9 on histone H3. Recent observations have shown oncogenic activity of JMJD2B. We explored the functional role of JMJD2B in cancer cell proliferation, survival and tumorigenesis, and determined its expression profile in gastric cancer. Knocking down JMJD2B expression by small interfering RNA (siRNA) in gastric and other cancer cells inhibited cell proliferation and/or induced apoptosis and elevated the expression of p53 and p21{sup CIP1} proteins. The enhanced p53 expression resulted from activation of the DNA damage response pathway. JMJD2B knockdown markedly suppressed xenograft tumor growth in vivo in mice. Moreover, JMJD2B expression was increased in primary gastric-cancer tissues of humans. Thus, JMJD2B is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of gastric cancer.

  13. Structural basis for the high Ca2+ affinity of the ubiquitous SERCA2b Ca2+ pump.

    Science.gov (United States)

    Vandecaetsbeek, Ilse; Trekels, Mieke; De Maeyer, Marc; Ceulemans, Hugo; Lescrinier, Eveline; Raeymaekers, Luc; Wuytack, Frank; Vangheluwe, Peter

    2009-11-03

    Sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) Ca(2+) transporters pump cytosolic Ca(2+) into the endoplasmic reticulum, maintaining a Ca(2+) gradient that controls vital cell functions ranging from proliferation to death. To meet the physiological demand of the cell, SERCA activity is regulated by adjusting the affinity for Ca(2+) ions. Of all SERCA isoforms, the housekeeping SERCA2b isoform displays the highest Ca(2+) affinity because of a unique C-terminal extension (2b-tail). Here, an extensive structure-function analysis of SERCA2b mutants and SERCA1a2b chimera revealed how the 2b-tail controls Ca(2+) affinity. Its transmembrane (TM) segment (TM11) and luminal extension functionally cooperate and interact with TM7/TM10 and luminal loops of SERCA2b, respectively. This stabilizes the Ca(2+)-bound E1 conformation and alters Ca(2+)-transport kinetics, which provides the rationale for the higher apparent Ca(2+) affinity. Based on our NMR structure of TM11 and guided by mutagenesis results, a structural model was developed for SERCA2b that supports the proposed 2b-tail mechanism and is reminiscent of the interaction between the alpha- and beta-subunits of Na(+),K(+)-ATPase. The 2b-tail interaction site may represent a novel target to increase the Ca(2+) affinity of malfunctioning SERCA2a in the failing heart to improve contractility.

  14. Affinity of ceftobiprole for penicillin-binding protein 2b in Streptococcus pneumoniae strains with various susceptibilities to penicillin.

    Science.gov (United States)

    Davies, Todd A; He, Wenping; Bush, Karen; Flamm, Robert K

    2010-10-01

    Wild-type penicillin-binding protein (PBP) 2b from penicillin-susceptible Streptococcus pneumoniae had high affinity for ceftobiprole and penicillin (50% inhibitory concentrations [IC(50)s] of ≤0.15 μg/ml) but not ceftriaxone (IC(50) of >8 μg/ml). In clinical isolates, ceftobiprole and PBP 2b affinities were reduced 15- to 30-fold with a Thr-446-Ala substitution and further still with an additional Ala-619-Gly PBP 2b substitution. Ceftobiprole remained active (MICs of ≤1 μg/ml) against all strains tested and behaved more like penicillin than ceftriaxone with respect to PBP 2b binding.

  15. Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats

    Science.gov (United States)

    Liang, Xiping; Wang, Sha; Qin, Guangcheng; Xie, Jingmei; Tan, Ge; Zhou, Jiying; McBride, Devin W.

    2017-01-01

    Tyrosine phosphorylation of NR2B (NR2B-pTyr), a subunit of the N-methyl-D-aspartate (NMDA) receptor, has been reported to develop central sensitization and persistent pain in the spine, but its effect in chronic migraines has not been examined. We hypothesized that tyrosine phosphorylation of NR2B contributes to chronic migraines (CM) through calcitonin gene-related peptide (CGRP) in rats. Ninety-four male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections. In a subset of animals, the time course and location of NR2B tyrosine phosphorylation were detected by western blot and immunofluorescence double staining. Another set of animals were given either genistein, vehicle, or genistein and recombinant CGRP. The mechanical threshold was measured, the expressions of NR2B-pTyr, NR2B, and CGRP were quantified using western blot, and nitric oxide (NO) was measured with the nitric acid reductase method. NR2B-pTyr expression, in neurons, peaked at 24 hours after CM. Genistein improved the mechanical threshold and reduced migraine attacks 24 and 72 hours after CM. Tyrosine phosphorylation of NR2B decreased the mechanical threshold and increased migraine attacks via upregulated CGRP expression in the rat model of CM. Thus, tyrosine phosphorylation of NR2B may be a potential therapeutic target for treatment of CM.

  16. The effect of NR2B subunit palmitoylation at the spinal level after chronic dorsal root ganglia compression in rats.

    Science.gov (United States)

    Xia, Tianjiao; Cui, Yin; Shi, Han; Ma, Zhengliang; Gu, Xiaoping

    2014-11-01

    The NR2B subunit (N-methyl-D-aspartate receptor 2B subunit) regulates the source of pain, and it participates in the formation of central sensitization. Palmitoylation was shown to be involved in the regulation of N-methyl-D-aspartate receptor internalization. In the present study, we investigated the effects of NR2B subunit palmitoylation in a chronic dorsal root ganglia compression (CCD) rat model. Paw mechanical withdrawal threshold and paw withdrawal thermal latency were used to assess mechanical allodynia and thermal hyperalgesia after a CCD operation and an intrathecal injection of the inhibitor of palmitoylation (2-bromopalmitate [2-BP]). The acyl-biotinyl exchange method, Western blotting, and coimmunoprecipitation were used to investigate the effects of pain processing and the expression of levels of NR2B palmitoylation and phosphorylation at the spinal level. CCD rats had long-lasting thermal hyperalgesia and mechanical allodynia, leading to upregulation of the level of NR2B palmitoylation and phosphorylation at the spinal level. An intrathecal treatment with 2-BP on day 14 after CCD surgery markedly improved pain behaviors and downregulated the expression of NR2B palmitoylation and phosphorylation. These data suggest that upregulated NR2B palmitoylation in CCD-induced neuropathic pain and intrathecal injection of 2-BP could reduce pain behaviors and NR2B phosphorylation. Our findings indicate that spinal NR2B palmitoylation is an important component of CCD-induced neuropathic pain, and it might be a potential target for chronic pain therapy.

  17. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection

    Directory of Open Access Journals (Sweden)

    Stephen Noel Waggoner

    2012-12-01

    Full Text Available The signaling lymphocyte activation molecule (SLAM family receptor, 2B4/CD244, was first implicated in anti-viral immunity by the discovery that mutations of the SLAM-associated protein, SAP/SH2D1A, impaired 2B4-dependent stimulation of T and natural killer (NK cell anti-viral functions in X-linked lymphoproliferative (XLP syndrome patients with uncontrolled Epstein-Barr virus (EBV infections. Engagement of 2B4 has been variably shown to either activate or inhibit lymphocytes which express this receptor. While SAP expression is required for stimulatory functions of 2B4 on lymphocytes, it remains unclear whether inhibitory signals derived from 2B4 can predominate even in the presence of SAP. Regardless, mounting evidence suggests that 2B4 expression by NK and CD8 T cells is altered by virus infection in mice as well as in humans, and 2B4-mediated signaling may be an important determinant of effective immune control of chronic virus infections. In this review, recent findings regarding the expression and function of 2B4 as well as SAP on T and NK cells during virus infection is discussed, with a focus on the role of 2B4-CD48 interactions in crosstalk between innate and adaptive immunity.

  18. Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling.

    Science.gov (United States)

    Xu, Fangxia; Zhao, Xin; Liu, Lin; Song, Jia; Zhu, Yingjun; Chu, Shuaishuai; Shao, Xueming; Li, Xiuxiu; Ma, Zhengliang; Gu, Xiaoping

    2017-09-06

    Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.

  19. Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats

    Directory of Open Access Journals (Sweden)

    Xiping Liang

    2017-01-01

    Full Text Available Tyrosine phosphorylation of NR2B (NR2B-pTyr, a subunit of the N-methyl-D-aspartate (NMDA receptor, has been reported to develop central sensitization and persistent pain in the spine, but its effect in chronic migraines has not been examined. We hypothesized that tyrosine phosphorylation of NR2B contributes to chronic migraines (CM through calcitonin gene-related peptide (CGRP in rats. Ninety-four male Sprague-Dawley rats were subjected to seven inflammatory soup (IS injections. In a subset of animals, the time course and location of NR2B tyrosine phosphorylation were detected by western blot and immunofluorescence double staining. Another set of animals were given either genistein, vehicle, or genistein and recombinant CGRP. The mechanical threshold was measured, the expressions of NR2B-pTyr, NR2B, and CGRP were quantified using western blot, and nitric oxide (NO was measured with the nitric acid reductase method. NR2B-pTyr expression, in neurons, peaked at 24 hours after CM. Genistein improved the mechanical threshold and reduced migraine attacks 24 and 72 hours after CM. Tyrosine phosphorylation of NR2B decreased the mechanical threshold and increased migraine attacks via upregulated CGRP expression in the rat model of CM. Thus, tyrosine phosphorylation of NR2B may be a potential therapeutic target for treatment of CM.

  20. High-throughput screening assays for CYP2B6 metabolism and inhibition using fluorogenic vivid substrates.

    Science.gov (United States)

    Marks, Bryan D; Goossens, Tony A; Braun, Heidi A; Ozers, Mary S; Smith, Ronald W; Lebakken, Connie; Trubetskoy, Olga V

    2003-01-01

    CYP2B6 is a highly polymorphic P450 isozyme involved in the metabolism of endo- and xenobiotics with known implications for the activation of many procarcinogens resulting in carcinogenesis. However, lack of validated high-throughput screening (HTS) CYP2B6 assays has limited the current understanding and full characterization of this isozyme's involvement in human drug metabolism. Here, we have developed and characterized a fluorescence-based HTS assay employing recombinant human CYP2B6 and 2 novel fluorogenic substrates (the Vivid CYP2B6 Blue and Cyan Substrates). Assay validation included testing the inhibitory potency of a panel of drugs and compounds known to be metabolized by this isozyme, including CYP2B6 substrates, inhibitors, and known inducers. Compound rankings based on inhibitory potency in the Vivid CYP2B6 Blue and Cyan Assays matched compound rankings based on relative affinity measurements from previously published data (K(i), K(d), or K(m) values) for the CYP2B6 isozyme. In conclusion, these assays are proven to be robust and sensitive, with broad dynamic ranges and kinetic parameters allowing screening in HTS mode of a large panel of compounds for CYP2B6 metabolism and inhibition, and are a valuable new tool for CYP2B6 studies.

  1. The L2b real-time PCR targeting the pmpH gene of Chlamydia trachomatis used for the diagnosis of lymphogranuloma venereum is not specific to L2b strains.

    Science.gov (United States)

    Touati, A; Peuchant, O; Hénin, N; Bébéar, C; de Barbeyrac, B

    2016-06-01

    The French Reference Centre for chlamydiae uses two real-time PCRs targeting the pmpH gene of Chlamydia trachomatis to differentiate between L strains and variant L2b, responsible for a lymphogranuloma venereum outbreak in Europe. We compared the results obtained for 122 L2b C. trachomatis-positive specimens, using the two real-time PCRs, with the sequencing of the ompA gene. Only 91 specimens were confirmed as L2b. Our results demonstrate that the lymphogranuloma venereum outbreak is no longer dominated by the variant L2b, and that many L-positive specimens were misidentified as L2b with the method used, which raises the question of its specificity. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Propofol inhibits LPS-induced apoptosis in lung epithelial cell line, BEAS-2B.

    Science.gov (United States)

    Lv, Xiang; Zhou, Xuhui; Yan, Jia; Jiang, Jue; Jiang, Hong

    2017-03-01

    Lipopolysaccharide (LPS) plays an important role in lung endothelial apoptosis which is crucial for lung fibrogenesis in ARDS progression. Reactive oxygen species (ROS) has been reported to be involved in LPS-induced lung epithelial cell apoptosis. Propofol is a commonly used intravenous anesthetic agent in clinic and it could attenuate LPS-induced epithelial cells oxidation and apoptosis. However, the mechanisms are still obscure. In this study, we examined whether and how propofol attenuates LPS-induced oxidation and apoptosis in BEAS-2B cells. Compared with control group, LPS up-regulated Pin-1, phosphatase A2 (PP2A) expression, induced p66(Shc)-Ser(36) phosphorylation, and facilitated p66(Shc) mitochondrial translocation, thus leading to superoxide anion (O2(-)) generation, mitochondrial cytochrome c release, active caspase 3 over-expression and cell viability inhibition. Importantly, propofol was shown to down-regulate LPS-induced PP2A expression, limit p66(Shc) mitochondrial translocation, decrease O2(-) generation, inhibit mitochondrial cytochrome c release, reduce active caspase 3 expression, and recover cells viability, while propofol had no effects on LPS-induced Pin-1 expression and p66(Shc)-Ser(36) phosphorylation. Moreover, the protective effects of propofol on LPS-induced BEAS-2B cells apoptosis were similar to that of calyculin A, which is an inhibitor of PP2A. We also found that FTY720, which is an activator of PP2A, can effectively reverse the protective function of propofol. Our data illustrated that propofol could alleviate LPS-induced BEAS-2B cells oxidation and apoptosis through down-regulating PP2A expression, limiting p66(Shc)-Ser(36) dephosphorylation and p66(Shc) mitochondrial translocation, decreasing O2(-) generation, mitochondrial cytochrome c release, activating caspase 3 expression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. The Preparation and Characterization of INTEC Phase 2b Composition Variation Study Glasses

    Energy Technology Data Exchange (ETDEWEB)

    B. A. Staples; B. A. Scholes; L. L. Torres; C. A. Musick; B. R. Boyle (INEEL); D. K. Peeler (SRTC); J. D. Vienna (PNNL)

    2000-02-01

    The second phase of the composition variation study (CVS) for the development of glass compositions to immobilize Idaho Nuclear Technology and Engineering Center (INTEC) high level wastes (HLW) is complete. This phase of the CVS addressed waste composition of high activity waste fractions (HAW) from the initial separations flowsheet. Updated estimates if INTEC calcined HLW compositions and of high activity waste fractions proposed to be separated from dissolved calcine were used as the waste component for this CVS phase. These wastes are of particular interest because high aluminum, calcium, zirconium, fluorine, potassium, and low iron and sodium content places them outside the vitrification experience in the Department of Energy complex. Because of the presence of calcium and fluorine, two major zirconia calcine components not addressed in Phase I, a series of scooping tests, designated Phase 2a, were performed. The results of these tests provided information on the effects of calcium and fluoride solubility and their impacts on product properties and composition boundary information for Phase 2b. Details and results of Phase 2a are reported separately. Through application of statistical techniques and the results of Phase 2a, a test matrix was defined for Phase 2b of the CVS. From this matrix, formulations were systematically selected for preparation and characterization with respect to visual and optical homogeneity, viscosity as a function of melt temperature, liquidus temperature (TL), and leaching properties based on response to the product consistency test. The results of preparing and characterizing the Phase 2b glasses are presented in this document. Based on the results, several formulations investigated have suitable properties for further development. A full analysis of the composition-product characteristic relationship of glasses being developed for immobilizing INTEC wastes will be performed at the completion of composition-property relationship

  4. Synthesis and optical properties of polycrystalline Li2Al2B2O7 (LABO)

    Science.gov (United States)

    Dagdale, S. R.; Muley, G. G.

    2016-05-01

    A polycrystalline lithium aluminum borate (Li2Al2B2O7, LABO) has been synthesized by using simple solid-state technique. The obtained LABO polycrystalline was characterized by powder X-ray diffraction; Fourier transform infrared (FT-IR) spectroscopy and second harmonic generation (SHG) efficiency measurement. The functional groups were identified using the FT-IR spectroscopic data. The SHG efficiency of the polycrystalline material was obtained by the classic Kurtz powder technique using a fundamental wavelength 1064 nm of Nd:YAG laser and it is found to be 1.4 times that of potassium dihydrogen phosphate (KDP).

  5. B2B inter-organisational digitalisation strategies - towards an interaction based approach

    DEFF Research Database (Denmark)

    Ivang, Reimer; Rask, Morten; Hinson, Robert

    2009-01-01

    Purpose: Digital technology is increasingly important for businesses as it has the capability to enable, support and sometimes influence the overall strategic direction of the corporation. This paper investigates b2b inter-organisational digitalisation strategies in one of Denmark's biggest...... utilising the digital technology successfully mostly organised their strategic work as described in the interaction approach to digitalisation strategy. Practical value: Study demonstrates a pragmatic route to deepening digitalization success in large firm with considerable e-business investments...... and implemented. Lastly this is one of the few studies utilizing degree of freedom analysis to understand digitalization strategy....

  6. Targeting Sulfotransferase (SULT) 2B1b as a Regulator of Cholesterol Metabolism in Prostate Cancer

    Science.gov (United States)

    2015-10-01

    designing a tet- inducible CRISPR /CAS9-based method to directly edit the genome by inserting LoxP sites flanking critical exon(s) in the SULT2b1b gene and...suppressed growth and greatly enhanced cell death, we performed further analysis to Figure 3. LNCaP cells were transfected with indicated siRNA...until we can generate the stable inducible cell lines using the CRISPR /CAS9 method described above in subtask 2. Major Task 4: Development  of

  7. Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

    Directory of Open Access Journals (Sweden)

    Phil M. Pithan

    2016-05-01

    Full Text Available Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states.

  8. Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

    Science.gov (United States)

    Pithan, Phil M; Decker, David; Sardo, Manlio Sutero; Viola, Giampietro

    2016-01-01

    Summary Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS) in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states. PMID:27340476

  9. A INFLUÊNCIA DA MARCA NO AMBIENTE ORGANIZACIONAL (B2B

    Directory of Open Access Journals (Sweden)

    Paulo Afonso Barbosa da Silveira

    2009-09-01

    Full Text Available Este artigo versa sobre a importância de uma marca forte no, cada dia mais competitivo, mercado organizacional (B2B e a sua influência no processo de venda corporativa. Serão apresentados alguns conceitos sobre marcas e delineado um breve histórico das mesmas, passando a uma análise sobre a evolução e valorização que as marcas vêm sofrendo ao longo do tempo, dando destaque à sua influência na tomada de decisão de compra no âmbito corporativo.

  10. The Analysis of B2B Business Model from the Viewpoint of Value Chain

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Electronic business impacts differently the busines s process in or between the corporations in variant degree. In view of the new fea tures of the internet, critical questions to be answered inclued: what are t he emerging business models and related to this, which strategic marketing appro aches are applied,or emerging. In the paper, the business models in B2B are clas sified into four types as e-procurement, e-marketplace, e-trade exchange, and collaborative trading community from the value viewpoint...

  11. Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-β Responses

    Science.gov (United States)

    Iqbal, Jawed; Ansari, Mairaj Ahmed; Kumar, Binod; Dutta, Dipanjan; Roy, Arunava; Chikoti, Leela; Pisano, Gina; Dutta, Sujoy; Veettil, Mohanan Valiya; Chandran, Bala

    2016-01-01

    IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation. Acetylated IFI16 also interacted with cytoplasmic STING and induced IFN-β. However, the identity of IFI16 associated nuclear proteins involved in STING activation and the mechanism is not known. Mass spectrometry of proteins precipitated by anti-IFI16 antibodies from uninfected endothelial cell nuclear lysate revealed that histone H2B interacts with IFI16. Single and double proximity ligation microscopy, immunoprecipitation, EdU-genome labeled virus infection, and chromatin immunoprecipitation studies demonstrated that H2B is associated with IFI16 and BRCA1 in the nucleus in physiological conditions. De novo KSHV and HSV-1 infection as well as latent KSHV and EBV infection induces the cytoplasmic distribution of H2B-IFI16, H2B-BRCA1 and IFI16-ASC complexes. Vaccinia virus (dsDNA) cytoplasmic replication didn’t induce the redistribution of nuclear H2B-IFI16 or H2B into the cytoplasm. H2B is critical in KSHV and HSV-1 genome recognition by IFI16 during de novo infection. Viral genome sensing by IFI16-H2B-BRCA1 leads to BRCA1 dependent recruitment of p300, and acetylation of H2B and IFI16. BRCA1 knockdown or inhibition of p300 abrogated the acetylation of H2B-IFI16 or H2B. Ran-GTP protein mediated the translocation of acetylated H2B and IFI16 to the cytoplasm along with BRCA1 that is independent of IFI16-ASC inflammasome. ASC knockdown didn’t affect the acetylation of H2B, its cytoplasmic

  12. 77 FR 10037 - Temporary Non-Agricultural Employment of H-2B Aliens in the United States

    Science.gov (United States)

    2012-02-21

    ... and Hour Division 29 CFR Part 503 Temporary Non-Agricultural Employment of H-2B Aliens in the United... Division 29 CFR Part 503 RIN 1205-AB58 Temporary Non-Agricultural Employment of H-2B Aliens in the United...

  13. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    Science.gov (United States)

    Cui, Yihui; Jin, Jing; Zhang, Xuliang; Xu, Hao; Yang, Liguo; Du, Dan; Zeng, Qingwen; Tsien, Joe Z; Yu, Huiting; Cao, Xiaohua

    2011-01-01

    Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  14. Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

    Science.gov (United States)

    Martinez, Fernando J; Pratt, Gabriel A; Van Nostrand, Eric L; Batra, Ranjan; Huelga, Stephanie C; Kapeli, Katannya; Freese, Peter; Chun, Seung J; Ling, Karen; Gelboin-Burkhart, Chelsea; Fijany, Layla; Wang, Harrison C; Nussbacher, Julia K; Broski, Sara M; Kim, Hong Joo; Lardelli, Rea; Sundararaman, Balaji; Donohue, John P; Javaherian, Ashkan; Lykke-Andersen, Jens; Finkbeiner, Steven; Bennett, C Frank; Ares, Manuel; Burge, Christopher B; Taylor, J Paul; Rigo, Frank; Yeo, Gene W

    2016-11-23

    HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs) demonstrate abnormal splicing changes, likely due to increased nuclear-insoluble hnRNP A2/B1. Mutant iPSC-MNs display decreased survival in long-term culture and exhibit hnRNP A2/B1 localization to cytoplasmic granules as well as exacerbated changes in gene expression and splicing upon cellular stress. Our findings provide a cellular resource and reveal RNA networks relevant to neurodegeneration, regulated by normal and mutant hnRNP A2/B1. VIDEO ABSTRACT.

  15. Functional characterization of cadmium-responsive garlic gene AsMT2b: A new member of metallothionein family

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A new gene of metallothionein (MT) family was cloned from garlic (Allium sativum) seedlings using RACE method and designated AsMT2b. The full length of AsMT2b cDNA was 520 bp encoding 80 amino acids. The deduced amino acids of AsMT2b showed that AsMT2b contained the characteristic structure of type 2 MT proteins, but the number and arrangement of the cysteine residues in the N- and C-terminal domains was different from other type 2 MT proteins. Semi-quantitative reverse transcriptase-PCR showed that transcript levels of AsMT2b were enhanced only in response to higher concentrations or longer incubation time of Cd. Such an expression pattern of AsMT2b greatly differed from that of other type 2 MT genes. Yeast cells transformed with this gene had improved resistance to Cd. AsMT2b overexpressing Arabidopsis showed stronger Cd tolerance and higher Cd accumulation compared with wild-type plants. These results suggest that AsMT2b should be useful in phytoremediation of Cd-polluted soil in the future.

  16. Involvement of AMPK in regulating the degradation of MAD2B under high glucose in neuronal cells.

    Science.gov (United States)

    Meng, Xianfang; Chu, Guangpin; Ye, Chen; Tang, Hui; Qiu, Ping; Hu, Yue; Li, Man; Zhang, Chun

    2016-12-13

    Although our recent study has demonstrated that mitotic spindle assembly checkpoint protein (MAD2B) mediates high glucose-induced neuronal apoptosis, the mechanisms for MAD2B degradation under hyperglycaemia have not yet been elucidated. In this study, we first found that the activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) was decreased in neurons, accompanied with the increased expression of MAD2B. Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B. Moreover, activation of AMPK prevented neuronal cells from high glucose-induced injury as demonstrated by the reduced expression of cyclin B1 and percentage of apoptosis as detected by TUNEL. We further found that when total protein synthesis was suppressed by chlorhexidine, the degradation of MAD2B was slower in high glucose-treated neurons and was mainly dependent on the ubiquitin-proteasome system. Finally, it was indicated that high glucose inhibited the ubiquitination of MAD2B, which could be reversed by activation of AMPK. Collectively, this study demonstrates that AMPK acts as a key regulator of MAD2B expression, suggesting that activation of AMPK signalling might be crucial for the treatment of high glucose-induced neuronal injury.

  17. Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors

    Directory of Open Access Journals (Sweden)

    Antonio Sanz-Clemente

    2013-03-01

    Full Text Available Synaptic activity triggers a profound reorganization of the molecular composition of excitatory synapses. For example, NMDA receptors are removed from synapses in an activity- and calcium-dependent manner, via casein kinase 2 (CK2 phosphorylation of the PDZ ligand of the GluN2B subunit (S1480. However, how synaptic activity drives this process remains unclear because CK2 is a constitutively active kinase, which is not directly regulated by calcium. We show here that activated CaMKII couples GluN2B and CK2 to form a trimolecular complex and increases CK2-mediated phosphorylation of GluN2B S1480. In addition, a GluN2B mutant, which contains an insert to mimic the GluN2A sequence and cannot bind to CaMKII, displays reduced S1480 phosphorylation and increased surface expression. We find that although disrupting GluN2B/CaMKII binding reduces synapse number, it increases synaptic-GluN2B content. Therefore, the GluN2B/CaMKII association controls synapse density and PSD composition in an activity-dependent manner, including recruitment of CK2 for the removal of GluN2B from synapses.

  18. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    Directory of Open Access Journals (Sweden)

    Yihui Cui

    Full Text Available Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP but did not alter long-term depression (LTD. The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  19. Identification of a novel NR2B-selective NMDA receptor antagonist using a virtual screening approach.

    Science.gov (United States)

    Mony, Laetitia; Triballeau, Nicolas; Paoletti, Pierre; Acher, Francine C; Bertrand, Hugues-Olivier

    2010-09-15

    We report the identification of a novel NR2B-selective NMDAR antagonist with an original scaffold, LSP10-0500. This compound was identified by a virtual high-throughput screening approach on the basis of a quantitative pharmacophore model of NR2B-specific NMDAR antagonists. A SAR study around LSP10-0500 is also described.

  20. Mitotic arrest deficient protein MAD2B is overexpressed in human glioma, with depletion enhancing sensitivity to ionizing radiation.

    Science.gov (United States)

    Zhao, Jun; Liu, Shuizhong; Wang, Hongwei; Zhang, Xiaomei; Kang, Tiejiang; Li, Zhanyi; Deng, Hemin; Yue, Wu; Cao, Shujie

    2011-06-01

    Mitotic arrest deficient protein MAD2B, an enzyme involved in translesion DNA synthesis, has been implicated in several cancers. However, its role in human glioma has not been defined. In the present study, we investigated the expression levels of MAD2B in human gliomas and normal brain tissues, and determined whether depletion of MAD2B enhanced the sensitivity of glioma cells to ionizing radiation. Using reverse transcription-polymerase chain reaction and immunohistochemical analysis, MAD2B was found to be overexpressed in glioma specimens compared with normal brain tissue. Silencing of MAD2B markedly reduced clonogenic survival of glioma cells and significantly enhanced apoptosis in response to ionizing radiation. This effect was associated with caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, disruption of MAD2B potentiated radiation-induced genomic damage, as evidenced by increased phosphorylation of gamma histone H2AX (γ-H2AX). Our findings reveal that expression of MAD2B is deregulated in glioma, and targeting MAD2B may be a potential strategy for improving the efficacy of radiotherapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Electronic structure and vibrational properties of KRbAl{sub 2}B{sub 2}O{sub 7}

    Energy Technology Data Exchange (ETDEWEB)

    Atuchin, V.V. [Laboratory of Optical Materials and Structures, Institute of Semiconductor Physics, SB RAS, Novosibirsk 90, 630090 (Russian Federation); Adichtchev, S.V. [Laboratory of Condensed Matter Spectroscopy, Institute of Automation and Electrometry, SB RAS, Novosibirsk 90, 630090 (Russian Federation); Bazarov, B.G.; Bazarova, Zh.G. [Laboratory of Oxide Systems, Baikal Institute of Nature Management, SB RAS, Ulan-Ude 47, 670047 (Russian Federation); Gavrilova, T.A. [Laboratory of Nanodiagnostics and Nanolithography, Institute of Semiconductor Physics, SB RAS, Novosibirsk 630090 (Russian Federation); Grossman, V.G. [Laboratory of Oxide Systems, Baikal Institute of Nature Management, SB RAS, Ulan-Ude 47, 670047 (Russian Federation); Kesler, V.G. [Laboratory of Physical Principles for Integrated Microelectronics, Institute of Semiconductor Physics, Novosibirsk, 630090 (Russian Federation); Meng, G.S. [Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Key Laboratory of Quantum Information, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230026 (China); Lin, Z.S., E-mail: zslin@mail.ipc.ac.cn [Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Surovtsev, N.V. [Laboratory of Condensed Matter Spectroscopy, Institute of Automation and Electrometry, SB RAS, Novosibirsk 90, 630090 (Russian Federation)

    2013-03-15

    Graphical abstract: With the KRbAl{sub 2}B{sub 2}O{sub 7} powder formed by solid state synthesis (left), Raman spectrum (right upper) and XPS valence electronic states (right lower) were measured, agreed with the first-principles results. Highlights: ► KRbAl{sub 2}B{sub 2}O{sub 7} powder was obtained by solid state synthesis. ► Vibrational properties of KRbAl{sub 2}B{sub 2}O{sub 7} were determined by unpolarized Raman spectrum. ► Electronic structures of KRbAl{sub 2}B{sub 2}O{sub 7} were measured by XPS. ► Experimental electronic structure is consistent with the first-principles result. ► KRbAl{sub 2}B{sub 2}O{sub 7} has a noticeable refractive indices increase and small NLO effects decrease compared to K{sub 2}Al{sub 2}B{sub 2}O{sub 7}. - Abstract: The physical properties of KRbAl{sub 2}B{sub 2}O{sub 7} have been considered in comparison with those of K{sub 2}Al{sub 2}B{sub 2}O{sub 7} and Rb{sub 2}Al{sub 2}B{sub 2}O{sub 7}. The vibrational parameters of KRbAl{sub 2}B{sub 2}O{sub 7} have been measured by Raman spectroscopy as very similar to those of K{sub 2}Al{sub 2}B{sub 2}O{sub 7}. The electronic structures of KRbAl{sub 2}B{sub 2}O{sub 7} have been evaluated by X-ray photoelectron spectroscopy and ab initio computations using CASTEP package. A noticeable refractive indices increase and small decrease of nonlinear optical properties have been found in KRbAl{sub 2}B{sub 2}O{sub 7} in reference to optical parameters of K{sub 2}Al{sub 2}B{sub 2}O{sub 7}.

  2. Expression of Cucumber mosaic virus suppressor 2b alters FWA methylation and its siRNA accumulation in Arabidopsis thaliana.

    Science.gov (United States)

    Hamera, Sadia; Yan, Youngsheng; Song, Xiaoguang; Chaudhary, Safee Ullah; Murtaza, Iram; Su, Lei; Tariq, Muhammad; Chen, Xiaoying; Fang, Rongxiang

    2016-11-15

    The Cucumber mosaic virus (CMV) suppressor 2b co-localizes with AGO4 in cytoplasmic and nuclear fractions of Arabidopsis thaliana Biochemical fractionation of A. thaliana cellular extracts revealed that 2b and AGO4 coexist in multiple size exclusions. 2b transgenic A. thaliana exhibited an enhanced accumulation of 24nt siRNAs from flowering wageningen (FWA) and other heterochromatic loci. These plants also exhibited hypo-methylation of an endogenous- as well as transgene-FWA promoter at non-CG sites. In corroboration, both transgenic 2b and CMV infection affected the regulation of transposons which mimics the ago4 phenotype. In conclusion, 2b perturbs plant defense by interfering with AGO4-regulated transcriptional gene silencing.

  3. Purification of FLAG-tagged eukaryotic initiation factor 2B complexes, subcomplexes, and fragments from Saccharomyces cerevisiae.

    Science.gov (United States)

    Mohammad-Qureshi, Sarah S; Haddad, Raphaël; Palmer, Karren S; Richardson, Jonathan P; Gomez, Edith; Pavitt, Graham D

    2007-01-01

    The eukaryotic initiation factor 2B (eIF2B) is a five-subunit guanine nucleotide exchange factor, that functions during translation initiation to catalyze the otherwise slow exchange of GDP for GTP on its substrate eIF2. Assays to measure substrate interaction and guanine nucleotide release ability of eIF2B require the complex to be purified free of interacting proteins. We have also found that a subcomplex of two subunits, gamma and epsilon or the largest one, epsilon alone, promotes this activity. Within eIF2Bepsilon, the catalytic center requires the C-terminal 200 residues only. Here, we describe our protocols for purifying the Saccharomyces cerevisiae eIF2B complexes and the catalytic subunit using FLAG-tagged proteins overexpressed in yeast cells. Using commercially available FLAG-affinity resin and high salt buffer, we are able to purify active eIF2B virtually free of contaminants.

  4. Growth, dielectric and nonlinear optical properties of Li3Cs2B5O10 single crystals

    Science.gov (United States)

    Sukumar, M.; Ramesh Babu, R.; Ramamurthi, K.

    2017-01-01

    Lithium cesium borate (Li3Cs2B5O10), an alkali metal borate, single crystals were grown by Czochralski method. Chemical etching was performed on grown Li3Cs2B5O10 crystal at various regions. The observed dislocation densities are varied at different regions of the grown Li3Cs2B5O10 crystal. Dielectric behavior of Li3Cs2B5O10 crystal at different temperatures is studied. The third-order nonlinear optical parameters of lithium cesium borate crystal are determined by Z-scan technique. The nonlinear refractive index ( n 2) value is estimated to be -7.272 × 10-11 cm2/W, and the corresponding third-order nonlinear susceptibility ( χ 3) is estimated to be 4.19 × 10-9 esu. The measured nonlinear refractive indices reveal the self-defocusing effect of Li3Cs2B5O10 crystal.

  5. Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors.

    Science.gov (United States)

    Pawlak, Robert; Melchor, Jerry P; Matys, Tomasz; Skrzypiec, Anna E; Strickland, Sidney

    2005-01-11

    Chronic ethanol abuse causes up-regulation of NMDA receptors, which underlies seizures and brain damage upon ethanol withdrawal (EW). Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors. tPA interacts with NR2B-containing NMDA receptors and is required for up-regulation of the NR2B subunit in response to ethanol. As a consequence, tPA-deficient mice have reduced NR2B, extracellular signal-regulated kinase 1/2 phosphorylation, and seizures after EW. tPA-mediated facilitation of EW seizures is abolished by NR2B-specific NMDA antagonist ifenprodil. These results indicate that tPA mediates the development of physical dependence on ethanol by regulating NR2B-containing NMDA receptors.

  6. SYNERGIC CYTOTOXICITY TO GASTRIC CANCER CELLS BY COMBINED USE OF TRICHOSANTHIN AND RECOMBINANT INTERFERON α-2B

    Institute of Scientific and Technical Information of China (English)

    胡梅洁; 张曙; 吴裕忻; 江石湖

    2000-01-01

    Objective To investigate a new approach of the combined use of trichosanthin (TCS) and recombinant interferon alpha - 2b (rIFN α - 2b) against digestive system cancer cells. Methods Detect separately the cytotoxicity of TCS, rIFN α-2b and their combination against digestive system cancer cell SGC-7901.Results In the experiment in vitro, TCS, rlFN α-2b both had direct, dose dependent cytotoxicity against SGC- 7901. Their combined use demonstrated a toxicity significantly higher than that of the two drugs used alone,showing a significant synergic effect. This synergic cytotoxicity was confirmed in the animal experiment.Conclusion Combined use of TCS and rIFN α- 2b decreases the therapeutic dose of TCS and its toxic adverse effect, and this synergic effect is favorable to the clinical use of TCS protein against gastric cancer.

  7. Thermal Decomposition of Anhydrous Alkali Metal Dodecaborates M2B12H12 (M = Li, Na, K

    Directory of Open Access Journals (Sweden)

    Liqing He

    2015-11-01

    Full Text Available Metal dodecaborates M2/nB12H12 are regarded as the dehydrogenation intermediates of metal borohydrides M(BH4n that are expected to be high density hydrogen storage materials. In this work, thermal decomposition processes of anhydrous alkali metal dodecaborates M2B12H12 (M = Li, Na, K synthesized by sintering of MBH4 (M = Li, Na, K and B10H14 have been systematically investigated in order to understand its role in the dehydrogenation of M(BH4n. Thermal decomposition of M2B12H12 indicates multistep pathways accompanying the formation of H-deficient monomers M2B12H12−x containing the icosahedral B12 skeletons and is followed by the formation of (M2B12Hzn polymers. The decomposition behaviors are different with the in situ formed M2B12H12 during the dehydrogenation of metal borohydrides.

  8. Expression of Cucumber mosaic virus suppressor 2b alters FWA methylation and its siRNA accumulation in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Sadia Hamera

    2016-11-01

    Full Text Available The Cucumber mosaic virus (CMV suppressor 2b co-localizes with AGO4 in cytoplasmic and nuclear fractions of Arabidopsis thaliana. Biochemical fractionation of A. thaliana cellular extracts revealed that 2b and AGO4 coexist in multiple size exclusions. 2b transgenic A. thaliana exhibited an enhanced accumulation of 24nt siRNAs from flowering wageningen (FWA and other heterochromatic loci. These plants also exhibited hypo-methylation of an endogenous- as well as transgene-FWA promoter at non-CG sites. In corroboration, both transgenic 2b and CMV infection affected the regulation of transposons which mimics the ago4 phenotype. In conclusion, 2b perturbs plant defense by interfering with AGO4-regulated transcriptional gene silencing.

  9. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Science.gov (United States)

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  10. High heat transfer oxidizer heat exchanger design and analysis. [RL10-2B engine

    Science.gov (United States)

    Kmiec, Thomas D.; Kanic, Paul G.; Peckham, Richard J.

    1987-01-01

    The RL10-2B engine, a derivative of the RL10, is capable of multimode thrust operation. This engine operates at two low thrust levels: tank head idle (THI), which is approximately 1 to 2% of full thrust, and pumped idle (PI), which is 10% of full thrust. Operation at THI provides vehicle propellant settling thrust and efficient engine thermal conditioning; PI operation provides vehicle tank pre-pressurization and maneuver thrust for low-g deployment. Stable combustion of the RL10-2B engine during the low thrust operating modes can be accomplished by using a heat exchanger to supply gaseous oxygen to the propellant injector. The oxidizer heat exchanger (OHE) vaporizes the liquid oxygen using hydrogen as the energy source. The design, concept verification testing and analysis for such a heat exchanger is discussed. The design presented uses a high efficiency compact core to vaporize the oxygen, and in the self-contained unit, attenuates any pressure and flow oscillations which result from unstable boiling in the core. This approach is referred to as the high heat transfer design. An alternative approach which prevents unstable boiling of the oxygen by limiting the heat transfer is referred to as the low heat transfer design and is reported in Pratt & Whitney report FR-19135-2.

  11. On the Apparent Orbital Inclination Change of the Extrasolar Transiting Planet TrES-2b

    CERN Document Server

    Scuderi, Louis J; Males, Jared R; Green, Elizabeth M; Close, Laird M

    2009-01-01

    On June 15, 2009 UT the transit of TrES-2b was detected using the University of Arizona's 1.55 meter Kuiper Telescope with 2.0-2.5 millimag RMS accuracy in the I-band. We find a central transit time of T_c = 2454997.76286 +/- 0.00035 HJD, an orbital period of P = 2.4706127 +/- 0.0000009 days, and an inclination angle of i = 83.92 +/- 0.05 degrees, which is consistent with our re-fit of the original I-band light curve of O'Donovan et al. (2006) where we find i = 83.84 +/- 0.05 degrees. We calculate an inclination change of Delta i = -0.08 +/- 0.071 degrees over the last 3 years, and as such, our observations rule out, at the ~11 sigma level, the apparent change of orbital inclination to i_predicted = 83.35 +/- 0.1 degrees as predicted by Mislis & Schmitt (2009) for our epoch. Indeed, we detect no significant changes in any of the orbital parameters of TrES-2b when comparing the original I-band light curve to our recent I-band light curve.

  12. Side effects in melanoma patients receiving adjuvant interferon alfa-2b therapy: a nurse's perspective.

    Science.gov (United States)

    Rubin, Krista M; Vona, Karen; Madden, Kathleen; McGettigan, Suzanne; Braun, Ilana M

    2012-08-01

    The aim of this review was to examine the toxicity profile of adjuvant interferon (IFN) alfa-2b in melanoma patients from a nursing perspective and to summarize practical information to guide the effective management of common IFN toxicities to improve patient comfort. This is a narrative summary of both research and review articles identified by searching PubMed, National Cancer Institute, and American Cancer Society websites. It also assesses recognized guidelines on the management of adjuvant IFN toxicity relevant to nurses who are caring for patients receiving adjuvant IFN therapy. Adjuvant high-dose IFN alfa-2b (HDI) as compared with observation significantly prolongs relapse-free survival in patients with melanoma at high risk for recurrence after surgical resection; however, treatment compliance and patient quality of life can be compromised by its toxicity profile. HDI toxicities affect a number of organ systems and the majority of patients will experience some side effects. Common toxicities such as flu-like symptoms, fatigue, anorexia, neuropsychiatric symptoms, and laboratory abnormalities are discussed, along with both pharmacological and nonpharmacological management strategies. The considerable side effects of HDI can be managed using established strategies. Oncology nurses play a significant role in the management of patients with melanoma receiving adjuvant HDI, and their prompt recognition of side effects, together with an understanding of effective pharmacological and nonpharmacological interventions, will improve patient comfort; this has the potential to positively influence treatment adherence and completion of the recommended treatment course.

  13. VHL type 2B mutations retain VBC complex form and function.

    Directory of Open Access Journals (Sweden)

    Kathryn E Hacker

    Full Text Available BACKGROUND: von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1alpha and HIF-2alpha, resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS: This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1alpha. CONCLUSIONS: Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.

  14. The influence of magnetocrystalline anisotropy on the magnetocaloric effect: A case study on Co 2 B

    Science.gov (United States)

    Fries, M.; Skokov, K. P.; Karpenkov, D. Yu.; Franco, V.; Ener, S.; Gutfleisch, O.

    2016-12-01

    The influence of magnetocrystalline anisotropy on the magnetocaloric effect (MCE) was studied on single crystals of Co2B and compared to measurements on polycrystalline samples. Large differences in adiabatic temperature change Δ T a d and magnetic entropy change Δ S M were found along the different crystallographic directions. The magnetocaloric effect differs by 40% in the case of Δ T a d in a field change of 1.9 T when applying the field along the hard axis and easy plane of magnetization. In the case of Δ S M , the values differ 50% and 35% from each other in field changes of 1 and 1.9 T, respectively. It was found that this anisotropy effect does not saturate in fields up to 4 T, which is higher than the anisotropy field of Co2B ( ≈2 T). A simple model was developed to illustrate the possible effect on magnetocrystalline anisotropy, showing large differences especially in application relevant fields of about 1 T. The results strongly suggest that the MCE could be maximized when orienting single crystalline powders in an easy axis parallel to the applied field in active magnetocaloric regenerator structures, and therefore the overall device efficiency could be increased.

  15. Textbook Evaluation: An Analysis of Listening Comprehension Parts in Top Notch 2A & 2B

    Directory of Open Access Journals (Sweden)

    Afshin Soori

    2015-10-01

    Full Text Available Textbooks are the instruments that assist both teachers and learners in process of second language learning. With respect to the importance of textbooks in a language course, evaluation of course books is a significant issue for most researchers. The present study investigated and analyzed Listening Comprehension parts in Top Notch 2A & 2B 2nd edition. Top Notch 2A & 2B have 10 Units. The number of listening comprehension parts is in the range of 2 to 4 parts in each unit through the book. So the number of listening comprehension parts is not equally distributed. The participants of this study are 10 EFL teachers of two English language Institutes in Jahrom. Strong and weak aspects of Listening Comprehension parts have indicated in this research. The weaknesses involve the pictures and visuals are not clear enough to enhance students' motivation and interest, the audio is not completely suitable for students' English level, and Discussion parts are not stimulating students' talking. Furthermore this study revealed the crucial function of teachers in listening achievement of students. Keywords: textbook evaluation, listening comprehension, ELT

  16. Sulfate as a pivotal factor in regulation of Serratia sp. strain S2B pigment biosynthesis.

    Science.gov (United States)

    Rastegari, Banafsheh; Karbalaei-Heidari, Hamid Reza

    2016-10-01

    In the present work, we investigated the prodiginine family as secondary metabolite members. Bacterial strain S2B, with the ability to produce red pigment, was isolated from the Sarcheshmeh copper mine in Iran. 16S rDNA gene sequencing revealed that the strain was placed in the Serratia genus. Pigment production was optimized using low-cost culture medium and the effects of various physicochemical factors were studied via statistical approaches. Purification of the produced pigment by silica gel column chromatography showed a strong red pigment fraction and a weaker orange band. Mass spectrometry, FT-IR spectroscopy and (1)H NMR analysis revealed that the red pigment was prodigiosin and the orange band was a prodigiosin-like analog, with molecular weights of 323 and 317 Da, respectively. Genotoxicity and cytotoxicity studies confirmed their membership in the prodiginine family. Analysis of the production pattern of the pigments in the presence of different concentrations of ammonium salts revealed the role of sulfate as an important factor in regulation of the pigment biosynthesis pathway. Overall, the data showed that regulation of the pigment biosynthesis pathway in Serratia sp. strain S2B was affected by inorganic micronutrients, particularly the sulfate ions.

  17. Isl2b regulates anterior second heart field development in zebrafish.

    Science.gov (United States)

    Witzel, Hagen R; Cheedipudi, Sirisha; Gao, Rui; Stainier, Didier Y R; Dobreva, Gergana D

    2017-01-20

    After initial formation, the heart tube grows by addition of second heart field progenitor cells to its poles. The transcription factor Isl1 is expressed in the entire second heart field in mouse, and Isl1-deficient mouse embryos show defects in arterial and venous pole development. The expression of Isl1 is conserved in zebrafish cardiac progenitors; however, Isl1 is required for cardiomyocyte differentiation only at the venous pole. Here we show that Isl1 homologues are expressed in specific patterns in the developing zebrafish heart and play distinct roles during cardiac morphogenesis. In zebrafish, isl2a mutants show defects in cardiac looping, whereas isl2b is required for arterial pole development. Moreover, Isl2b controls the expression of key cardiac transcription factors including mef2ca, mef2cb, hand2 and tbx20. The specific roles of individual Islet family members in the development of distinct regions of the zebrafish heart renders this system particularly well-suited for dissecting Islet-dependent gene regulatory networks controlling the behavior and function of second heart field progenitors in distinct steps of cardiac development.

  18. Bright optical dayside emission from extrasolar planet CoRoT-2b

    CERN Document Server

    Snellen, I A G; Burrows, A

    2009-01-01

    We present our analysis of the red-channel CoRoT data of extrasolar planet CoRoT-2b. A deep secondary eclipse is detected at a level of 1.02+-0.20x10^-4, which suggests that all of the planet-signal detected previously in white light by Alonso et al. (2009) originates from the red channel. CoRoT-2b is the coolest exoplanet that has been detected in the optical so far. In contrast to the other planets, its measured brightness temperature of 2170+-50 K is significantly higher than its maximum hemisphere-averaged effective day-side temperature. However, it is not expected that a hot Jupiter radiates as a black body, and its thermal spectrum can deviate significantly from a Planck curve. We present models of the planet/star flux ratio as function of wavelength, which are calculated for a T/P profile in radiative and hydrostatic equilibrium, using a self-consistent atmosphere code. These are compared with the CoRoT detection. We estimate that reflected light contributes only at a 10-20% level to the total optical ...

  19. Canine parvovirus-2b-associated erythema multiforme in a litter of English Setter dogs.

    Science.gov (United States)

    Woldemeskel, Moges; Liggett, Alan; Ilha, Marcia; Saliki, Jeremiah T; Johnson, Leslie P

    2011-05-01

    Erythema multiforme (EM) was diagnosed in a litter of English Setter puppies. The puppies developed erythematous cutaneous lesions at the age of 2 weeks. Microscopically, there was individual keratinocyte apoptosis associated with lymphocyte exocytosis in all layers of the epidermis. Intranuclear viral inclusions were seen in multiple tissues and organs. Tissues from the tongue, lymph node, spleen, skin, and small intestine were positive for Canine parvovirus-2 (CPV-2) and negative for Canine distemper virus (CDV) and Canid herpesvirus 1 by fluorescent antibody test. Negative-staining electron microscopy detected parvovirus particles in the intestinal contents. The skin and small intestine were positive for CPV-2b and negative for CDV by polymerase chain reaction. The mucocutaneous junctions and small intestines stained positive for CPV by immunohistochemistry. The present report documents CPV-2b-associated EM in a litter of English Setters and substantiates the single previous report associating EM with CPV-2. The finding suggests that CPV should be considered as a possible cause of EM in dogs.

  20. Role of extrachromosomal histone H2B on recognition of DNA viruses and cell damage

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    Kouji eKobiyama

    2013-05-01

    Full Text Available Histones are essential components of chromatin structure, and histone modification plays an important role in various cellular functions including transcription, gene silencing and immunity. Histones also play distinct roles in extrachromosomal settings. Extrachromosomal histone H2B acts as a cytosolic sensor to detect double-stranded DNA (dsDNA fragments derived from infectious agents or damaged cells to activate innate and acquired immune responses in various cell types. It also physically interacts with interferon (IFN-β promoter stimulator 1 (IPS-1, an essential adaptor molecule that activates innate immunity, through COOH-terminal importin 9-related adaptor organizing histone H2B and IPS-1 (CIAO, resulting in a distinct signaling complex that induces dsDNA-induced type I IFN production. Such a molecular platform acts as a cellular sensor to recognize aberrant dsDNA in cases of viral infection and cell damage. This mechanism may also play roles in autoimmunity, transplantation rejection, gene-mediated vaccines, and other therapeutic applications.

  1. Genetic variability of CYP2B6 polymorphisms in four southern Chinese populations

    Institute of Scientific and Technical Information of China (English)

    Bing-Ying Xu; Ming-Liang He; Li-Ping Guo; Shui-Shan Lee; Qing-Ming Dong; Yi Tan; Hong Yao; Li-Hua Li; Che-Kit Lin; Hsiang-Fu Kung

    2007-01-01

    AIM: To investigate the genotype and allelic frequencies of Cytochrome P450 2B6 polymorphisms in four southern Chinese populations.METHODS: DNA was obtained from blood samples from Han Chinese from Hong Kong and three minority groups,the Wa, Bulang and Lahu from Yunnan in southern China. Genotyping was performed using real-time PCR and confirmed by direct sequencing.RESULTS: A total of 507 subjects from southern China were studied. Results showed there is a high prevalence of 516G > T (34.5%) in ethnic Chinese compared to literature reports on other Asian populations and Caucasians. The frequency of the 516TT genotype is higher in the Hah majority (23.1%) than in three other ethnic minority groups (i.e., 7.4%, 9.1% and 15.8%) in southern China.CONCLUSION: This was the first study to document the spectrum of CYP2B6 allelic variants and genotypes in a southern Chinese population. The 516G > T allele is associated with a defective metabolism of efavirenz (EFV), which therefore may predispose to drug toxicity.Treatment regimens for human immunodeficiency virus (HIV) and heroin addiction may need to be optimized in different populations because of the marked variability of the key metabolizing enzyme.

  2. Summary report on the fuel performance modeling of the AFC-2A, 2B irradiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Pavel G. Medvedev

    2013-09-01

    The primary objective of this work at the Idaho National Laboratory (INL) is to determine the fuel and cladding temperature history during irradiation of the AFC-2A, 2B transmutation metallic fuel alloy irradiation experiments containing transuranic and rare earth elements. Addition of the rare earth elements intends to simulate potential fission product carry-over from pyro-metallurgical reprocessing. Post irradiation examination of the AFC-2A, 2B rodlets revealed breaches in the rodlets and fuel melting which was attributed to the release of the fission gas into the helium gap between the rodlet cladding and the capsule which houses six individually encapsulated rodlets. This release is not anticipated during nominal operation of the AFC irradiation vehicle that features a double encapsulated design in which sodium bonded metallic fuel is separated from the ATR coolant by the cladding and the capsule walls. The modeling effort is focused on assessing effects of this unanticipated event on the fuel and cladding temperature with an objective to compare calculated results with the temperature limits of the fuel and the cladding.

  3. Genome-wide function of H2B ubiquitylation in promoter and genic regions.

    Science.gov (United States)

    Batta, Kiran; Zhang, Zhenhai; Yen, Kuangyu; Goffman, David B; Pugh, B Franklin

    2011-11-01

    Nucleosomal organization in and around genes may contribute substantially to transcriptional regulation. The contribution of histone modifications to genome-wide nucleosomal organization has not been systematically evaluated. In the present study, we examine the role of H2BK123 ubiquitylation, a key regulator of several histone modifications, on nucleosomal organization at promoter, genic, and transcription termination regions in Saccharomyces cerevisiae. Using high-resolution MNase chromatin immunoprecipitation and sequencing (ChIP-seq), we map nucleosome positioning and occupancy in mutants of the H2BK123 ubiquitylation pathway. We found that H2B ubiquitylation-mediated nucleosome formation and/or stability inhibits the assembly of the transcription machinery at normally quiescent promoters, whereas ubiquitylation within highly active gene bodies promotes transcription elongation. This regulation does not proceed through ubiquitylation-regulated histone marks at H3K4, K36, and K79. Our findings suggest that mechanistically similar functions of H2B ubiquitylation (nucleosome assembly) elicit different functional outcomes on genes depending on its positional context in promoters (repressive) versus transcribed regions (activating).

  4. TUBB2B Mutation in an Adult Patient with Myoclonus-Dystonia

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    Joshua T. Geiger

    2017-08-01

    Full Text Available Background: Tubulin mutations are a cause of neuronal migrational disorders referred to as tubulinopathies. Mutations in tubulin genes can have a severe impact on microtubule function and result in heterogeneous clinical presentations. Current understanding of the clinical spectrum of tubulinopathies is predominantly based on research in fetal tissue and early-childhood cases. Methods: Testing of candidate genes followed by whole-exome sequencing was performed in an adult woman with a neurodevelopmental, hyperkinetic movement disorder, to identify the underlying genetic cause. Bioinformatic modeling and a systematic review of literature was conducted to investigate genotype-phenotype correlations. Results: The patient was found to carry a heterozygous, de novo c.722G>A, p.R241H mutation in a conserved domain of TUBB2B, encoding the β-isoform of tubulin. In silico analysis indicated that this mutation was pathogenic. On neuroimaging, the patient had asymmetric pachygyria and dysmorphic basal ganglia. Her neurological examination demonstrated mild cognitive impairment, myoclonus-dystonia, and skeletal anomalies. Conclusions: Here, we report the unique phenotype of an adult TUBB2B mutation carrier. This case illustrates a relatively mild phenotype compared to previously described fetal and early childhood cases. This highlights the importance of obtaining molecular genetic testing in individuals with a high probability of a genetic disease, including undiagnosed adult patients.

  5. Efficacy of interferon alpha-2b and lamivudine therapy for chronic hepatitis B in children

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To evaluate the efficacy of interferon (IFN) alpha-2b and lamivudine therapy in children with chronic hepatitis B virus (HBV) infection.Method Ten children who developed chronic hepatitis B infection received IFN alpha-2b 10 million international units (IU)/m2 body surface area, subcutaneously three times a week for six months. IFN+lamivudine therapy began to be used in the cases who were unresponsive to IFN treatment. Results Among 27 HBsAg (+) subjects in this study, interferon treatment was given to 11 subjects who developed chronic hepatitis. One case was excluded from the study due to detection of Herpes type 1 encephalitis. At the end of six months of follow-up, complete response was obtained in three (30%) patients and partial response in four (40%) patients, whereas no response was detected in three (30%) patients. Fifty percent of the cases experienced serological response, 70% biochemical response, and all (100%) had histological response. In three cases started concomitant IFN+lamivudine therapy, HBV-DNA became negative at the second month of treatment. Conclusions IFN-alpha and lamivudine can be used for the treatment of chronic hepatitis B infection in children.

  6. Population-specific regulation of Chmp2b by Lbx1 during onset of synaptogenesis in lateral association interneurons.

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    Jun Xu

    Full Text Available Chmp2b is closely related to Vps2, a key component of the yeast protein complex that creates the intralumenal vesicles of multivesicular bodies. Dominant negative mutations in Chmp2b cause autophagosome accumulation and neurodegenerative disease. Loss of Chmp2b causes failure of dendritic spine maturation in cultured neurons. The homeobox gene Lbx1 plays an essential role in specifying postmitotic dorsal interneuron populations during late pattern formation in the neural tube. We have discovered that Chmp2b is one of the most highly regulated cell-autonomous targets of Lbx1 in the embryonic mouse neural tube. Chmp2b was expressed and depended on Lbx1 in only two of the five nascent, Lbx1-expressing, postmitotic, dorsal interneuron populations. It was also expressed in neural tube cell populations that lacked Lbx1 protein. The observed population-specific expression of Chmp2b indicated that only certain population-specific combinations of sequence specific transcription factors allow Chmp2b expression. The cell populations that expressed Chmp2b corresponded, in time and location, to neurons that make the first synapses of the spinal cord. Chmp2b protein was transported into neurites within the motor- and association-neuropils, where the first synapses are known to form between E11.5 and E12.5 in mouse neural tubes. Selective, developmentally-specified gene expression of Chmp2b may therefore be used to endow particular neuronal populations with the ability to mature dendritic spines. Such a mechanism could explain how mammalian embryos reproducibly establish the disynaptic cutaneous reflex only between particular cell populations.

  7. Vagal afferent-dependent cholecystokinin modulation of visceral pain requires central amygdala NMDA-NR2B receptors in rats.

    Science.gov (United States)

    Wang, E M; Li, W T; Yan, X J; Chen, X; Liu, Q; Feng, C C; Cao, Z J; Fang, J Y; Chen, S L

    2015-09-01

    Cholecystokinin (CCK), a gut hormone that is released during feeding, exerts gastrointestinal effects in part through vagal pathway. It is reported to be a potential trigger for increased postprandial visceral sensitivity in healthy subjects and, especially in patients with irritable bowel syndrome. NR2B-containing N-methyl-d-aspartate (NMDA) receptors in the central amygdala (CeA) participate in pain modulation. Systemically administered CCK activates the CeA-innervating neurons. Here, we investigated whether CCK modulation of visceral sensitivity is mediated through CeA NMDA-NR2B receptors and whether this modulation involves vagal pathway. We first examined the visceromotor response (VMR) to colorectal distention (CRD) following i.p. injection of CCK octapeptide (CCK-8) in a rat model. Next, the NR2B antagonist ifenprodil and the NR2A antagonist NVP-AAM077 were microinjected into the CeA before systemic CCK injection. NR2B phosphorylation was detected by Western blot. To down-regulate NR2B gene expression, NR2B-specific small interfering RNA (siRNA) was delivered into CeA neurons by electroporation. In addition, the effects of functional deafferentation by perivagal application of capsaicin and pretreatment with the CCK1 receptor antagonist devazepide were investigated. CCK-8 increased VMR to CRD in a dose-dependent manner. This effect was blunted by intra-CeA administration of ifenprodil (but not NVP-AAM077) and was accompanied by phosphorylation of NR2B subunits in the CeA. CCK failed to increase VMR to CRD in NR2B siRNA-treated rats. Perivagal capsaicin application and pretreatment with devazepide prevented CCK-induced pronociception and CeA NR2B phosphorylation. The pronociception induced by systemic CCK, which is vagal afferent-dependent, requires activation of CeA NMDA-NR2B receptors. © 2015 John Wiley & Sons Ltd.

  8. RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis.

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    Chun-mei Liang

    Full Text Available BACKGROUND: Many publications have evaluated the correlation between RET, PHOX2B polymorphisms and Hirschsprung's disease with conflicting results. We performed this meta-analysis to clarify the association of RET, PHOX2B polymorphisms with HSCR. METHODS: We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. The combined odds ratio (OR with 95% CI was calculated to estimate the strength of the association. Heterogeneity and publication bias were also assessed. RESULTS: In total, 16 studies concerning RET and 4 studies concerning PHOX2B were included in the meta-analysis. The effects of five polymorphisms of RET (rs1800858, rs1800860, rs1800861, rs10900297, rs2435357 and one polymorphism (rs28647582 of PHOX2B were evaluated. We found a significant correlation between RET polymorphisms and HSCR. For rs1800858, the overall ORs (95% CI of the A versus G, AA versus GG, AA/AG versus GG and AA versus GG/AG were 3.81 (2.28-6.35; 8.36 (3.45-20.25; 3.59 (1.83-7.02; and 6.60 (3.66-11.89. For rs1800861, the comparison of subjects in the G versus T, GG versus TT, GG/TG versus TT and GG versus TT/TG were 2.85(1.81-4.47; 5.38(2.68-10.80; 3.07(2.17-4.34 and 4.14(1.84-9.30 respectively. For rs10900297, the comparison results showed statistically significant. (OR(C versus A = 5.05,95%CI = 4.16-6.13; OR(CC versus AA = 9.73, 95%CI = 5.94-15.94; OR(CC/AC versus AA = 5.31, 95%CI = 3.27-6.82; OR(CC versus AC/AA = 7.06,95%CI = 5.60-8.91. But, for rs1800860, the GG/GA versus AA did not reach statistical association (OR = 3.77, 95% CI = 0.94-15.07 and the G versus A, GG versus AA, GG versus GA/AA were 2.23 (1.60-3.11;4.56 (1.14-18.27; 2.38 (1.66-3.43 respectively. For rs2435357, the T versus C, TT versus CC, TT/TC versus CC and TT versus CC/TC were 4.53 (3.27-6.27; 11.44 (5.67-23.10; 4.04 (2.92-5.57, and 9.01(5.25-15.46.The single polymorphism of PHOX2B gene wasn't related to the risk

  9. ORBITAL PHASE VARIATIONS OF THE ECCENTRIC GIANT PLANET HAT-P-2b

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Nikole K.; Showman, Adam P. [Department of Planetary Sciences and Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Knutson, Heather A.; Desert, Jean-Michel; Kao, Melodie [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Cowan, Nicolas B. [Center for Interdisciplinary Exploration and Research in Astrophysics and Department of Physics and Astronomy, Northwestern University, 2131 Tech Drive, Evanston, IL 60208 (United States); Laughlin, Gregory; Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Burrows, Adam; Bakos, Gaspar A.; Hartman, Joel D. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Deming, Drake [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Crepp, Justin R. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States); Mighell, Kenneth J. [National Optical Astronomy Observatories, Tucson, AZ 85726 (United States); Agol, Eric [Department of Astronomy, University of Washington, Seattle, WA 98195 (United States); Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Fischer, Debra A. [Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Hinkley, Sasha; Johnson, John Asher [Department of Astrophysics, California Institute of Technology, MC 249-17, Pasadena, CA 91125 (United States); Howard, Andrew W., E-mail: nklewis@mit.edu [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); and others

    2013-04-01

    We present the first secondary eclipse and phase curve observations for the highly eccentric hot Jupiter HAT-P-2b in the 3.6, 4.5, 5.8, and 8.0 {mu}m bands of the Spitzer Space Telescope. The 3.6 and 4.5 {mu}m data sets span an entire orbital period of HAT-P-2b (P = 5.6334729 d), making them the longest continuous phase curve observations obtained to date and the first full-orbit observations of a planet with an eccentricity exceeding 0.2. We present an improved non-parametric method for removing the intrapixel sensitivity variations in Spitzer data at 3.6 and 4.5 {mu}m that robustly maps position-dependent flux variations. We find that the peak in planetary flux occurs at 4.39 {+-} 0.28, 5.84 {+-} 0.39, and 4.68 {+-} 0.37 hr after periapse passage with corresponding maxima in the planet/star flux ratio of 0.1138% {+-} 0.0089%, 0.1162% {+-} 0.0080%, and 0.1888% {+-} 0.0072% in the 3.6, 4.5, and 8.0 {mu}m bands, respectively. Our measured secondary eclipse depths of 0.0996% {+-} 0.0072%, 0.1031% {+-} 0.0061%, 0.071%{sub -0.013%}{sup +0.029,} and 0.1392% {+-} 0.0095% in the 3.6, 4.5, 5.8, and 8.0 {mu}m bands, respectively, indicate that the planet cools significantly from its peak temperature before we measure the dayside flux during secondary eclipse. We compare our measured secondary eclipse depths to the predictions from a one-dimensional radiative transfer model, which suggests the possible presence of a transient day side inversion in HAT-P-2b's atmosphere near periapse. We also derive improved estimates for the system parameters, including its mass, radius, and orbital ephemeris. Our simultaneous fit to the transit, secondary eclipse, and radial velocity data allows us to determine the eccentricity (e = 0.50910 {+-} 0.00048) and argument of periapse ({omega} = 188. Degree-Sign 09 {+-} 0. Degree-Sign 39) of HAT-P-2b's orbit with a greater precision than has been achieved for any other eccentric extrasolar planet. We also find evidence for a long

  10. Renormalized Volume

    CERN Document Server

    Gover, A Rod

    2016-01-01

    For any conformally compact manifold with hypersurface boundary we define a canonical renormalized volume functional and compute an explicit, holographic formula for the corresponding anomaly. For the special case of asymptotically Einstein manifolds, our method recovers the known results. The anomaly does not depend on any particular choice of regulator, but the coefficients of divergences do. We give explicit formulae for these divergences valid for any choice of regulating hypersurface; these should be relevant to recent studies of quantum corrections to entanglement entropies. The anomaly is expressed as a conformally invariant integral of a local Q-curvature that generalizes the Branson Q-curvature by including data of the embedding. In each dimension this canonically defines a higher dimensional generalization of the Willmore energy/rigid string action. We show that the variation of these energy functionals is exactly the obstruction to solving a singular Yamabe type problem with boundary data along the...

  11. Mutagenesis of D80-82 and G83 Residues in West Nile Virus NS2B: Effects on NS2B-NS3 Activity and Viral Replication

    Institute of Scientific and Technical Information of China (English)

    Fan Jia; Jingjing Fan; Bo Zhang; Zhiming Yuan

    2013-01-01

    Flaviviral NS2B is a required cofactor for NS3 serine protease activity and plays an important role in promoting functional NS2B-NS3 protease configuration and maintaining critical interactions with protease catalysis substrates.The residues D80DDG in West Nile virus (WNV) NS2B are important for protease activity.To investigate the effects of D80DDG in NS2B on protease activity and viral replication,the negatively charged region D80DD and the conserved residue G83 of NS2B were mutated (D80DD/E80EE,D80DD/K80KK,D80DD/A80AA,G83F,G83S,G83D,G83K,and G83A),and NS3 D75A was designated as the negative control.The effects of the mutations on NS2B-NS3 activity,viral translation,and viral RNA replication were analyzed using kinetic analysis of site-directed enzymes and a transient replicon assay.All substitutions resulted in significantly decreased enzyme activity and blocked RNA replication.The negative charge of D80DD is not important for maintaining NS2B function,but side chain changes in G83 have dramatic effects on protease activity and RNA replication.These results demonstrate that NS2B is important for viral replication and that D80DD and G83 substitutions prevent replication; they will be useful for understanding the relationship between NS2B and NS3.

  12. Estrogen receptor alpha, fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17beta-estradiol in MCF-7 cells.

    Science.gov (United States)

    Hu, Dong Gui; Mackenzie, Peter I

    2009-08-01

    UDP-glucuronosyltransferase 2B15 and 2B17 expression is up-regulated by 17beta-estradiol in MCF-7 breast cancer cells, as assessed by quantitative real-time polymerase chain reaction. Using 5'-deletion mapping and site-directed mutagenesis, we demonstrate that 17beta-estradiol activation of UGT2B15 gene transcription is mediated by a 282-base pair fragment positioned -454 to -172 nucleotides from the translation start site. This region contains two putative activator protein-1 (AP-1) elements, one imperfect estrogen response element (ERE), and two consensus ERE half-sites. We propose that these five sites act as an estrogen response unit (ERU), because mutation in any site reduces activation of the UGT2B15 promoter by 17beta-estradiol. Despite the presence of two AP-1 elements, the UGT2B15 promoter is not responsive to the AP-1 activator phorbol 12-myristate 13-acetate. Although electrophoretic mobility shift assays (EMSA) indicate that the AP-1 proteins c-Jun and Fos-related antigen 2 (Fra-2) bound to the distal AP-1 site, binding of Jun or Fos family members to the proximal AP-1 site was not detected by EMSA. Chromatin immunoprecipitation assays showed a 17beta-estradiol-induced recruitment of estrogen receptor (ER) alpha, c-Jun, and Fra-2 to the 282-bp ERU. The involvement of these three transcription factors in the stimulation of UGT2B15 gene expression by 17beta-estradiol was confirmed by siRNA silencing experiments. Mutagenesis and siRNA experiments indicate that UGT2B17 expression is also regulated by 17beta-estradiol via the ERU, which is fully conserved in both promoters. Because UGT2B15 and UGT2B17 inactivate steroid hormones by glucuronidation, the regulation of their genes by 17beta-estradiol may maintain steroid hormone homeostasis and prevent excessive estrogen signaling activity.

  13. Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax.

    Science.gov (United States)

    Cong, Haolong; Du, Ning; Yang, Yang; Song, Lei; Zhang, Wenliang; Tien, Po

    2016-11-01

    To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XL abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B

  14. Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Fan Guocai

    2010-07-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. Methods Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1. The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. Results We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. Conclusions This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization

  15. Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells

    Directory of Open Access Journals (Sweden)

    Helena Libalova

    2016-11-01

    Full Text Available This study used toxicogenomics to identify the complex biological response of human lung BEAS-2B cells treated with organic components of particulate matter in the exhaust of a diesel engine. First, we characterized particles from standard diesel (B0, biodiesel (methylesters of rapeseed oil in its neat form (B100 and 30% by volume blend with diesel fuel (B30, and neat hydrotreated vegetable oil (NEXBTL100. The concentration of polycyclic aromatic hydrocarbons (PAHs and their derivatives in organic extracts was the lowest for NEXBTL100 and higher for biodiesel. We further analyzed global gene expression changes in BEAS-2B cells following 4 h and 24 h treatment with extracts. The concentrations of 50 µg extract/mL induced a similar molecular response. The common processes induced after 4 h treatment included antioxidant defense, metabolism of xenobiotics and lipids, suppression of pro-apoptotic stimuli, or induction of plasminogen activating cascade; 24 h treatment affected fewer processes, particularly those involved in detoxification of xenobiotics, including PAHs. The majority of distinctively deregulated genes detected after both 4 h and 24 h treatment were induced by NEXBTL100; the deregulated genes included, e.g., those involved in antioxidant defense and cell cycle regulation and proliferation. B100 extract, with the highest PAH concentrations, additionally affected several cell cycle regulatory genes and p38 signaling.

  16. TFAP2B influences the effect of dietary fat on weight loss under energy restriction.

    Directory of Open Access Journals (Sweden)

    Tanja Stocks

    Full Text Available BACKGROUND: Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. METHODS AND FINDINGS: Randomized controlled trial of 771 obese adults. ( REGISTRATION: ISRCTN25867281. One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat% in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6 greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1 greater weight loss on the high-fat (interaction p-value; p = 0.00007. The replication study showed a similar (non-significant interaction pattern. Waist reduction results generally were similar. Study-strengths include (i the discovery study randomised trial design combined with the replication opportunity (ii the strict dietary intake control in both studies (iii the large sample sizes of both studies. Limitations are (i the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii the different interventions preventing identical replication-discovery study designs (iii some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed. CONCLUSIONS: Under energy restriction, TFAP2B may modify the effect of dietary fat intake on

  17. Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    PN; Rao; Abraham; Koshy; Jacob; Philip; Narayanan; Premaletha; Joy; Varghese; Krishnasamy; Narayanasamy; Samir; Mohindra; Nitin; Vikas; Pai; Manoj; Kumar; Agarwal; Ashokna; Konar; Hasmukh; B; Vora

    2014-01-01

    AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.

  18. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells.

    Directory of Open Access Journals (Sweden)

    Deborah Frenkel

    2016-07-01

    Full Text Available After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/- retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK cell-mediated cytotoxicity: i B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/- and FcγRIIIa deficient (CD16-/- C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii administration of NK1.1 specific IgG2a (mAb PK136 but not irrelevant IgG2a (myeloma M9144 prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei

  19. TFAP2B influences the effect of dietary fat on weight loss under energy restriction.

    Science.gov (United States)

    Stocks, Tanja; Angquist, Lars; Banasik, Karina; Harder, Marie N; Taylor, Moira A; Hager, Jörg; Arner, Peter; Oppert, Jean-Michel; Martinez, J Alfredo; Polak, Jan; Rousseau, Francis; Langin, Dominique; Rössner, Stephan; Holst, Claus; MacDonald, Ian A; Kamatani, Yoichiro; Pfeiffer, Andreas F H; Kunesova, Marie; Saris, Wim H M; Hansen, Torben; Pedersen, Oluf; Astrup, Arne; Sørensen, Thorkild I A

    2012-01-01

    Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. Randomized controlled trial of 771 obese adults. ( ISRCTN25867281.) One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat%) in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat (interaction p-value; p = 0.00007). The replication study showed a similar (non-significant) interaction pattern. Waist reduction results generally were similar. Study-strengths include (i) the discovery study randomised trial design combined with the replication opportunity (ii) the strict dietary intake control in both studies (iii) the large sample sizes of both studies. Limitations are (i) the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii) the different interventions preventing identical replication-discovery study designs (iii) some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed. Under energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction.

  20. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes.

    Science.gov (United States)

    Arendt, Maja; Fall, Tove; Lindblad-Toh, Kerstin; Axelsson, Erik

    2014-10-01

    High amylase activity in dogs is associated with a drastic increase in copy numbers of the gene coding for pancreatic amylase, AMY2B, that likely allowed dogs to thrive on a relatively starch-rich diet during early dog domestication. Although most dogs thus probably digest starch more efficiently than do wolves, AMY2B copy numbers vary widely within the dog population, and it is not clear how this variation affects the individual ability to handle starch nor how it affects dog health. In humans, copy numbers of the gene coding for salivary amylase, AMY1, correlate with both salivary amylase levels and enzyme activity, and high amylase activity is related to improved glycemic homeostasis and lower frequencies of metabolic syndrome. Here, we investigate the relationship between AMY2B copy numbers and serum amylase activity in dogs and show that amylase activity correlates with AMY2B copy numbers. We then describe how AMY2B copy numbers vary in individuals from 20 dog breeds and find strong breed-dependent patterns, indicating that the ability to digest starch varies both at the breed and individual level. Finally, to test whether AMY2B copy number is strongly associated with the risk of developing diabetes mellitus, we compare copy numbers in cases and controls as well as in breeds with varying diabetes susceptibility. Although we see no such association here, future studies using larger cohorts are needed before excluding a possible link between AMY2B and diabetes mellitus.