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Sample records for multiple over-expression experiments

  1. A fast and efficient gene-network reconstruction method from multiple over-expression experiments

    Directory of Open Access Journals (Sweden)

    Thurner Stefan

    2009-08-01

    Full Text Available Abstract Background Reverse engineering of gene regulatory networks presents one of the big challenges in systems biology. Gene regulatory networks are usually inferred from a set of single-gene over-expressions and/or knockout experiments. Functional relationships between genes are retrieved either from the steady state gene expressions or from respective time series. Results We present a novel algorithm for gene network reconstruction on the basis of steady-state gene-chip data from over-expression experiments. The algorithm is based on a straight forward solution of a linear gene-dynamics equation, where experimental data is fed in as a first predictor for the solution. We compare the algorithm's performance with the NIR algorithm, both on the well known E. coli experimental data and on in-silico experiments. Conclusion We show superiority of the proposed algorithm in the number of correctly reconstructed links and discuss computational time and robustness. The proposed algorithm is not limited by combinatorial explosion problems and can be used in principle for large networks.

  2. GroEL-GroES assisted folding of multiple recombinant proteins simultaneously over-expressed in Escherichia coli.

    Science.gov (United States)

    Goyal, Megha; Chaudhuri, Tapan K

    2015-07-01

    Folding of aggregation prone recombinant proteins through co-expression of chaperonin GroEL and GroES has been a popular practice in the effort to optimize preparation of functional protein in Escherichia coli. Considering the demand for functional recombinant protein products, it is desirable to apply the chaperone assisted protein folding strategy for enhancing the yield of properly folded protein. Toward the same direction, it is also worth attempting folding of multiple recombinant proteins simultaneously over-expressed in E. coli through the assistance of co-expressed GroEL-ES. The genesis of this thinking was originated from the fact that cellular GroEL and GroES assist in the folding of several endogenous proteins expressed in the bacterial cell. Here we present the experimental findings from our study on co-expressed GroEL-GroES assisted folding of simultaneously over-expressed proteins maltodextrin glucosidase (MalZ) and yeast mitochondrial aconitase (mAco). Both proteins mentioned here are relatively larger and aggregation prone, mostly form inclusion bodies, and undergo GroEL-ES assisted folding in E. coli cells during over-expression. It has been reported that the relative yield of properly folded functional forms of MalZ and mAco with the exogenous GroEL-ES assistance were comparable with the results when these proteins were overexpressed alone. This observation is quite promising and highlights the fact that GroEL and GroES can assist in the folding of multiple substrate proteins simultaneously when over-expressed in E. coli. This method might be a potential tool for enhanced production of multiple functional recombinant proteins simultaneously in E. coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction...... previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely...

  4. Over-expression of multiple cytochrome P450 genes in fenvalerate-resistant field strains of Helicoverpa armigera from north of China.

    Science.gov (United States)

    Xu, Li; Li, Dongzhi; Qin, Jianying; Zhao, Weisong; Qiu, Lihong

    2016-09-01

    Pyrethroid resistance was one of the main reasons for control failure of cotton bollworm Helicoverpa armigera (Hübner) in China. The promotion of Bt crops decreased the application of chemical insecticides in controlling H.armigera. However, the cotton bollworm still kept high levels of resistance to fenvalerate. In this study, the resistance levels of 8 field-collected strains of H. armigera from north of China to 4 insecticides, as well as the expression levels of related P450 genes were investigated. The results of bioassay indicated that the resistance levels to fenvalerate in the field strains varied from 5.4- to 114.7-fold, while the resistance levels to lambda-cyhalothrin, phoxim and methomyl were low, which were ranged from 1.5- to 5.2-, 0.2- to 1.6-, and 2.9- to 8.3- fold, respectively, compared to a susceptible strain. Synergistic experiment showed that PBO was the most effective synergist in increasing the sensitivity of H. armigera to fenvalerate, suggesting that P450 enzymes were involved in the pyrethroid resistance in the field strains. The results of quantitative RT-PCR indicated that eight P450 genes (CYP332A1, CYP4L11, CYP4L5, CYP4M6, CYP4M7, CYP6B7, CYP9A12, CYP9A14) were all significantly overexpressed in Hejian1 and Xiajin1 strains of H. armigera collected in 2013, and CYP4L5 was significantly overexpressed in all the 6 field strains collected in 2014. CYP332A1, CYP6B7 and CYP9A12 had very high overexpression levels in all the field strains, indicating their important roles in fenvalerate resistance. The results suggested that multiple P450 genes were involved in the high-level fenvalerate-resistance in different field strains of H. armigera collected from north of China. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The INEL beryllium multiplication experiment

    International Nuclear Information System (INIS)

    Smith, J.R.; King, J.J.

    1991-03-01

    The experiment to measure the multiplication of 14-MeV neutrons in bulk beryllium has been completed. The experiment consists of determining the ratio of 56 Mn activities induced in a large manganese bath by a central 14-MeV neutron source, with and without a beryllium sample surrounding the source. In the manganese bath method a neutron source is placed at the center of a totally-absorbing aqueous solution of MnSo 4 . The capture of neutrons by Mn produces a 56 Mn activity proportional to the emission rate of the source. As applied to the measurement of the multiplication of 14- MeV neutrons in bulk beryllium, the neutron source is a tritium target placed at the end of the drift tube of a small deuteron accelerator. Surrounding the source is a sample chamber. When the sample chamber is empty, the neutrons go directly to the surrounding MnSO 4 solution, and produce a 56 Mn activity proportional to the neutron emission rate. When the chamber contains a beryllium sample, the neutrons first enter the beryllium and multiply through the (n,2n) process. Neutrons escaping from the beryllium enter the bath and produce a 56 Mn activity proportional to the neutron emission rate multiplied by the effective value of the multiplication in bulk beryllium. The ratio of the activities with and without the sample present is proportional to the multiplication value. Detailed calculations of the multiplication and all the systematic effects were made with the Monte Carlo program MCNP, utilizing both the Young and Stewart and the ENDF/B-VI evaluations for beryllium. Both data sets produce multiplication values that are in excellent agreement with the measurements for both raw and corrected values of the multiplication. We conclude that there is not real discrepancy between experimental and calculated values for the multiplication of neutrons in bulk beryllium. 12 figs., 11 tabs., 18 refs

  6. The LBL multiple beam experiments

    International Nuclear Information System (INIS)

    Fessenden, T.J.; Keefe, D.; Kim, C.; Meuth, H.; Warwick, A.

    1987-01-01

    The multiple-beam induction linac approach to a heavy ion driver for inertial confinement fusion features continuous current amplification along the accelerator and a minimum of beam manipulations from source to pellet. Current amplification and bunch length control require careful shaping of the accelerating voltages. MBE-4 is designed as a four-beam induction linac that models much of the accelerator physics of the electrostatically focused section of a significantly longer induction accelerator. Four space-charge-dominated Cs + beams, initially about one meter in length at a current of 13 mA, are focused by electrostatic quadrupoles and accelerated in parallel from 200 to nearly 600 keV. The energy will reach approximately one MeV when the accelerator is complete. Experiments have proceeded in parallel with the construction of the apparatus which began in FY 85 and is now more than half complete. The results show a current amplification, so far, by a factor of 2.8 in good agreement with the longitudinal acceleration calculations. 9 refs

  7. ASSISTments Dataset from Multiple Randomized Controlled Experiments

    Science.gov (United States)

    Selent, Douglas; Patikorn, Thanaporn; Heffernan, Neil

    2016-01-01

    In this paper, we present a dataset consisting of data generated from 22 previously and currently running randomized controlled experiments inside the ASSISTments online learning platform. This dataset provides data mining opportunities for researchers to analyze ASSISTments data in a convenient format across multiple experiments at the same time.…

  8. Experiment of neutron multiplication in lead

    International Nuclear Information System (INIS)

    Jiang Wenmian; Chen Yuan; Liu Rong; Guo Haiping; Shen Jian

    1994-01-01

    The experiments of neutron multiplication in bulk lead have been performed with a total absorption detector (TAD). A hollow polyethylene sphere is used as neutron moderator and absorber of the TAD, which inner and outer diameters are 56 cm and 138 cm respectively. Slow neutron density in TAD is detected with a 6 Li glass scintillator. For Pb thicknesses of 5, 10, 15, 19.6 and 23.1 cm, the neutron multiplications are 1.301, 1.492, 1.599, 1.713 and 1.745 respectively. Overall experimental error is 2.7%. The calculational neutron multiplications with the 1-D ANISN code and ENDF/B-VI file are agreed with experimental ones within experimental error. Moreover, some factors of systematic error of TAD were investigated experimentally, but obvious factors have not been observed yet. (author)

  9. Initial experiments with Multiple Musical Gestures

    DEFF Research Database (Denmark)

    Jensen, Kristoffer; Graugaard, Lars

    2005-01-01

    The classic orchestra has a diminishing role in society, while hard-disc recorded music plays a predominant role today. A simple to use pointer interface in 2D for producing music is presented as a means for playing in a social situation. The sounds of the music are produced by a low-level...... synthesizer, and the music is produced by simple gestures that are repeated easily. The gestures include left-to-right and right-to-left motion shapes for spectral envelope and temporal envelope of the sounds, with optional backwards motion for the addition of noise; downward motion for note onset and several...... other manipulation gestures. The initial position controls which parameter is being affected, the notes intensity is controlled by the downward gesture speed, and a sequence is finalized instantly with one upward gesture. The synthesis employs a novel interface structure, the multiple musical gesture...

  10. Multiplicity: An Explorative Interview Study on Personal Experiences of People with Multiple Selves.

    Science.gov (United States)

    Ribáry, Gergő; Lajtai, László; Demetrovics, Zsolt; Maraz, Aniko

    2017-01-01

    Background and aims: Personality psychology research relies on the notion that humans have a single self that is the result of the individual's thoughts, feelings, and behaviors that can be reliably described (i.e., through traits). People who identify themselves as "multiple" have a system of multiple or alternative, selves, that share the same physical body. This is the first study to explore the phenomenon of multiplicity by assessing the experiences of people who identify themselves as "multiple." Methods: First, an Internet forum search was performed using the terms "multiplicity" and "multiple system." Based on that search, people who identified themselves as multiple were contacted. Interviews were conducted by a consultant psychiatrist, which produced six case vignettes. Results: Multiplicity is discussed on Twitter, Tumblr, Google+ and several other personal websites, blogs, and forums maintained by multiples. According to the study's estimates, there are 200-300 individuals who participate in these forums and believe they are multiple. Based on the six interviews, it appears that multiples have several selves who are relatively independent of each other and constitute the personality's system. Each "resident person" or self, has their own unique behavioral pattern, which is triggered by different situations. However, multiples are a heterogeneous group in terms of their system organization, memory functions, and control over switching between selves. Conclusions: Multiplicity can be placed along a continuum between identity disturbance and dissociative identity disorder (DID), although most systems function relatively well in everyday life. Further research is needed to explore this phenomenon, especially in terms of the extent to which multiplicity can be regarded as a healthy way of coping.

  11. Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia.

    Science.gov (United States)

    Song, Wei; Su, Haixiang; Song, Sisi; Paudel, Hemant K; Schipper, Hyman M

    2006-03-01

    Glial heme oxygenase-1 is over-expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up-regulation of HO-1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO-1 induction promotes mitochondrial oxidative stress, assays for 8-epiPGF(2alpha) (ELISA), protein carbonyls (ELISA) and 8-OHdG (HPLC-EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole-cell compartments derived from cultured rat astroglia engineered to over-express human (h) HO-1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [3H] thymidine incorporation and total cell counts. In rat astrocytes, hHO-1 over-expression (x 3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 microM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up-regulation of HO-1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme-derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO-1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. Copyright 2005 Wiley-Liss, Inc.

  12. Experiences of patients with multiple sclerosis from group counseling

    OpenAIRE

    Mazaheri, Mina; Fanian, Nasrin; Zargham-Boroujeni, Ali

    2011-01-01

    BACKGROUND: Group counseling is one of the most important methods in somatic and psychological rehabilitation of the multiple sclerosis (M.S.) patients. Knowing these patients? experiences, feelings, believes and emotion based on learning in group is necessary to indicate the importance of group discussion on quality of life of the patients. This study was done to achieve experiences of M.S. patients from group training. METHODS: This was a qualitative study using phenomenological method. The...

  13. Multiplicity: An Explorative Interview Study on Personal Experiences of People with Multiple Selves

    Directory of Open Access Journals (Sweden)

    Gergő Ribáry

    2017-06-01

    Full Text Available Background and aims: Personality psychology research relies on the notion that humans have a single self that is the result of the individual's thoughts, feelings, and behaviors that can be reliably described (i.e., through traits. People who identify themselves as “multiple” have a system of multiple or alternative, selves, that share the same physical body. This is the first study to explore the phenomenon of multiplicity by assessing the experiences of people who identify themselves as “multiple.”Methods: First, an Internet forum search was performed using the terms “multiplicity” and “multiple system.” Based on that search, people who identified themselves as multiple were contacted. Interviews were conducted by a consultant psychiatrist, which produced six case vignettes.Results: Multiplicity is discussed on Twitter, Tumblr, Google+ and several other personal websites, blogs, and forums maintained by multiples. According to the study's estimates, there are 200–300 individuals who participate in these forums and believe they are multiple. Based on the six interviews, it appears that multiples have several selves who are relatively independent of each other and constitute the personality's system. Each “resident person” or self, has their own unique behavioral pattern, which is triggered by different situations. However, multiples are a heterogeneous group in terms of their system organization, memory functions, and control over switching between selves.Conclusions: Multiplicity can be placed along a continuum between identity disturbance and dissociative identity disorder (DID, although most systems function relatively well in everyday life. Further research is needed to explore this phenomenon, especially in terms of the extent to which multiplicity can be regarded as a healthy way of coping.

  14. The experiences of individuals with Multiple Sclerosis in the Western ...

    African Journals Online (AJOL)

    Background: Multiple Sclerosis (MS) is a debilitating and degenerative lifelong neurological disease that seems to be growing increasingly more prevalent in South Africa. Objectives: The aim of this qualitative study was to explore the personal experiences of individuals with MS in the South African context. The focus of this ...

  15. Computer simulation of FT-NMR multiple pulse experiment

    Science.gov (United States)

    Allouche, A.; Pouzard, G.

    1989-04-01

    Using the product operator formalism in its real form, SIMULDENS expands the density matrix of a scalar coupled nuclear spin system and simulates analytically a large variety of FT-NMR multiple pulse experiments. The observable transverse magnetizations are stored and can be combined to represent signal accumulation. The programming language is VAX PASCAL, but a MacIntosh Turbo Pascal Version is also available.

  16. Computer simulation of FT-NMR multiple pulse experiment

    International Nuclear Information System (INIS)

    Allouche, A.; Pouzard, G.

    1989-01-01

    Using the product operator formalism in its real form, SIMULDENS expands the density matrix of a scalar coupled nuclear spin system and simulates analytically a large variety of FT-NMR multiple pulse experiments. The observable transverse magnetizations are stored and can be combined to represent signal accumulation. The programming language is VAX PASCAL, but a MacIntosh Turbo Pascal Version is also available. (orig.)

  17. Upper limits from counting experiments with multiple pipelines

    International Nuclear Information System (INIS)

    Sutton, Patrick J

    2009-01-01

    In counting experiments, one can set an upper limit on the rate of a Poisson process based on a count of the number of events observed due to the process. In some experiments, one makes several counts of the number of events, using different instruments, different event detection algorithms or observations over multiple time intervals. We demonstrate how to generalize the classical frequentist upper limit calculation to the case where multiple counts of events are made over one or more time intervals using several (not necessarily independent) procedures. We show how different choices of the rank ordering of possible outcomes in the space of counts correspond to applying different levels of significance to the various measurements. We propose an ordering that is matched to the sensitivity of the different measurement procedures and show that in typical cases it gives stronger upper limits than other choices. As an example, we show how this method can be applied to searches for gravitational-wave bursts, where multiple burst-detection algorithms analyse the same data set, and demonstrate how a single combined upper limit can be set on the gravitational-wave burst rate.

  18. Over-expression of DSCAM and COL6A2 cooperatively generates congenital heart defects.

    Directory of Open Access Journals (Sweden)

    Tamar R Grossman

    2011-11-01

    Full Text Available A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS, which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD, and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders.

  19. Multiple tracing experiments in unsaturated fractured clayey till

    DEFF Research Database (Denmark)

    Mortensen, Annette Pia; Jensen, Karsten Høgh; Nilsson, B.

    2004-01-01

    control of the water balance in the block. Experiments at three different steady-state flow rates were performed. Multiple tracers with different diffusion coefficients were applied in each experiment to evaluate the influence of diffusive exchange between fractures and the matrix. The tracers included...... a fast peak was followed by a long tailing period. At flow rates, two of the applied tracers revealed a double peak breakthrough curve, whereas the tracer with the lowest molecular diffusion coefficient showed only one peak. The separation of the tracers was hypothesized to be influenced by extensive...... two halogen anions ( Cl- and Br-), two fluorobenzoic acids (FBA) ( 2,3-DFBA and 2,6-DFBA), two fluorescent dyes (uranine and sulforhodamine B), and one colloidal tracer (0.5-mum mlatex particles). At high flow rates, the obtained tracer breakthrough showed a traditional asymmetrical behavior where...

  20. Experiences of patients with multiple sclerosis from group counseling.

    Science.gov (United States)

    Mazaheri, Mina; Fanian, Nasrin; Zargham-Boroujeni, Ali

    2011-01-01

    Group counseling is one of the most important methods in somatic and psychological rehabilitation of the multiple sclerosis (M.S.) patients. Knowing these patients' experiences, feelings, believes and emotion based on learning in group is necessary to indicate the importance of group discussion on quality of life of the patients. This study was done to achieve experiences of M.S. patients from group training. This was a qualitative study using phenomenological method. The samples were selected using purposeful sampling. Ten patients from M.S. society who had passed group training were included in the study. The group training was done through seven sessions weekly and voluntarily. The participants were interviewed using in-depth interview. The average time of each interview was between 30-50 minutes which has been recorded digitally and moved to a compact disc to transcribe and analysis. The data analyzed using 7-step Colaizzi method. The data were transformed into 158 codes, 12 sub-concepts and 4 main concepts including emotional consequences, communication, quality of life and needs. M.S can lead to multiple problems in patients such as somatic, behavioral, emotional and social disorders. Group psychotherapy is one of the methods which can decrease these problems and improve rehabilitation of the patients. Group discussion helps patients to overcome adverse feelings, behaviors and thoughts and guides them to move in a meaningful life. It also can improve quality of life and mental health of the patients.

  1. Over-Expression, Purification and Crystallization of Human Dihydrolipoamide Dehydrogenase

    Science.gov (United States)

    Hong, Y. S.; Ciszak, Ewa; Patel, Mulchand

    2000-01-01

    crystallization, E3 samples were prepared with and without His-tag. To minimize the aggregation of E3, apo- and holo- forms of E3s were tested, as well as a mutated E3. Dynamic light scattering measurements revealed that the E3 preparations without His-tag and substrate are highly monodispersive with regard to homodimers. Consequent crystallization trials of this E3 preparation led to single crystals of E3 grown by the vapor diffusion method. Crystals were obtained within a few days from solution containing poly (ethylene glycol) monomethyl ether 5000 as a precipitant. Autoindexing and integration of the X-ray diffraction data showed that E3 crystals belong to an orthorhombic system with unit cell parameters a-- 123. 1, b= 165.3 and c=214.3A. Further optimization of protein preparation and crystallization experiments for the structural determination will be discussed.

  2. Over-expression of HER-2 is associated with the stage in ...

    African Journals Online (AJOL)

    Background: The frequency of over-expression of human epidermal growth factor receptor-2 (HER-2) in bladder cancer is one of the highest among all human malignancies. This over-expression is thought to play a role in aberrant proliferation of cancer cells. Studies on HER-2 expression in bladder carcinoma have shown ...

  3. Multiple condensation induced water hammer events, experiments and theoretical investigations

    International Nuclear Information System (INIS)

    Barna, Imre Ferenc; Ezsoel, Gyoergy

    2011-01-01

    We investigate steam condensation induced water hammer (CIWH) phenomena and present experimental and theoretical results. Some of the experiments were performed in the PMK-2 facility, which is a full-pressure thermalhydraulic model of the nuclear power plant of VVER-440/312 type and located in the Atomic Energy Research Institute Budapest, Hungary. Other experiments were done in the ROSA facility in Japan. On the theoretical side CIWH is studied and analyzed with the WAHA3 model based on two-phase flow six first-order partial differential equations that present one dimensional, surface averaged mass, momentum and energy balances. A second order accurate high-resolution shockcapturing numerical scheme was applied with different kind of limiters in the numerical calculations. The applied two-fluid model shows some similarities to RELAP5 which is widely used in the nuclear industry to simulate nuclear power plant accidents. New features are the existence of multiple, independent CIWH pressure peaks both in experiments and in simulations. Experimentally measured and theoretically calculated CIWH pressure peaks are in qualitative agreement. However, the computational results are very sensitive against flow velocity. (orig.)

  4. Multiple Payload Ejector for Education, Science and Technology Experiments

    Science.gov (United States)

    Lechworth, Gary

    2005-01-01

    The education research community no longer has a means of being manifested on Space Shuttle flights, and small orbital payload carriers must be flown as secondary payloads on ELV flights, as their launch schedule, secondary payload volume and mass permits. This has resulted in a backlog of small payloads, schedule and cost problems, and an inability for the small payloads community to achieve routine, low-cost access to orbit. This paper will discuss Goddard's Wallops Flight Facility funded effort to leverage its core competencies in small payloads, sounding rockets, balloons and range services to develop a low cost, multiple payload ejector (MPE) carrier for orbital experiments. The goal of the MPE is to provide a low-cost carrier intended primarily for educational flight research experiments. MPE can also be used by academia and industry for science, technology development and Exploration experiments. The MPE carrier will take advantage of the DARPAI NASA partnership to perform flight testing of DARPA s Falcon small, demonstration launch vehicle. The Falcon is similar to MPE fiom the standpoint of focusing on a low-cost, responsive system. Therefore, MPE and Falcon complement each other for the desired long-term goal of providing the small payloads community with a low-cost ride to orbit. The readiness dates of Falcon and MPE are complementary, also. MPE is being developed and readied for flight within 18 months by a small design team. Currently, MPE is preparing for Critical Design Review in fall 2005, payloads are being manifested on the first mission, and the carrier will be ready for flight on the first Falcon demonstration flight in summer, 2006. The MPE and attached experiments can weigh up to 900 lb. to be compatible with Falcon demonstration vehicle lift capabilities fiom Wallops, and will be delivered to the Falcon demonstration orbit - 100 nautical mile circular altitude.

  5. Objectives and configuration of the Multiple Pulse Propagation Experiment

    International Nuclear Information System (INIS)

    Orzechowski, T.J.; Caporaso, G.J.; Chamber, F.W.; Chong, Y.P.; Deadrick, F.J.; Guethlein, G.; Fawley, W.M.; Renbarger, V.L.; Rogers, D. Jr.; Weir, J.T.; Eckstrom, D.; Stalder, K.; Hubbard, R.; Lee, P.

    1990-01-01

    The Multiple Pulse Propagation Experiment (MPPE) was designed to determine the hose stability properties of an intense relativistic electron beam in a beam generated density channel and to investigate range extension with increasing pulse number in the burst. This experiment used a 10-MeV electron beam generated by the Advanced Test Accelerator (ATA). The electron beam current was expected to be at least 6-kA with an equilibrium radius of 0.5 cm (RMS) in the gas. This last constraint implied an unnormalized, RMS beam emittance of 20 mrad-cm. In order to achieve beam stability against hose, each electron beam pulse had to be tailored in emittance in order to phase mix damp the instability. The initial offsets of the beam were to be kept small in order to prevent a large saturated amplitude. Numerical simulations determined the initial criteria for the emittance profile and initial beam displacements. In order to demonstrate a final density depression of 25% of ambient pressure, at least five pulses with interpulse separation of 1- to 2-ms were specified

  6. Youth experiences with multiple types of prejudice-based harassment.

    Science.gov (United States)

    Bucchianeri, Michaela M; Gower, Amy L; McMorris, Barbara J; Eisenberg, Marla E

    2016-08-01

    Despite prejudice-based harassment's associations with serious physical and mental health risks, research examining multiple forms of harassment among children/adolescents is lacking. This study documents the prevalence of prejudice-based harassment (i.e., harassment on the basis of gender, race/ethnicity, weight or physical appearance, sexual orientation, and disability status) among a large, statewide, school-based Midwestern U.S. sample of 162,034 adolescents. Weight-/appearance-based harassment was most prevalent among both girls (25.3%) and boys (19.8%). Adolescents from certain vulnerable groups experienced higher rates of multiple types of harassment, even when controlling for other sociodemographic characteristics. Prejudice-based harassment experiences are prevalent among adolescent girls and boys. Differential rates of each type of harassment are reported across groups within the corresponding sociodemographic status (e.g., white female adolescents report a significantly lower rate of race-based harassment (4.8%), as compared to Native American (18.6%), mixed/other race (18.9%), Hispanic/Latina (21.5%), Asian/Pacific Islander (24.2%), or Black/African American (24.8%) female adolescents); but a pattern of cross-harassment also is evident, such that differences in prevalence of each harassment type emerge across a variety of statuses (e.g., disability-based harassment was statistically significantly higher among discordant heterosexual (12.7%), gay (13.0%), bisexual (15.3%), and unsure (15.3%) male adolescents than among heterosexual male (7.2%) adolescents). Adolescents from specific sociodemographic groups are particularly vulnerable to certain types of harassment. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  7. Neutron multiplication in lead in the experiments with neutron generators

    International Nuclear Information System (INIS)

    Markovskij, D.V.

    1989-01-01

    A calculational analysis of neutron multiplication in lead, including the estimates of multiplication limits for the standard ENDF/BIV data set and the effects of various changes in the data themselves is performed. 10 refs, 5 figs

  8. Interpretation of the TRADE In-Pile source multiplication experiments

    International Nuclear Information System (INIS)

    Mercatali, Luigi; Carta, Mario; Peluso, Vincenzo

    2006-01-01

    Within the framework of the neutronic characterization of the TRIGA RC-1 reactor in support to the TRADE (TRiga Accelerator Driven Experiment) program, the interpretation of the subcriticality level measurements performed in static regime during the TRADE In-Pile experimental program is presented. Different levels of subcriticality have been measured using the MSA (Modified Source Approximated) method by the insertion of a standard fixed radioactive source into different core positions. Starting from a reference configuration, fuel elements were removed: control rods were moved outward as required for the coupling experiments envisioned with the proton accelerator and fission chambers were inserted in order to measure subcritical count rates. A neutron-physics analysis based on the modified formulation of the source multiplication method (MSM) has been carried out, which requires the systematic solution for each experimental configuration of the homogeneous, both in the forward and adjoint forms, and inhomogeneous Boltzmann equations. By means of such a methodology calculated correction factors to be applied to the MSA measured reactivities were produced in order to take into account spatial and energetic effects creating changes in the detector efficiencies and effective source with respect to the calibration configuration. The methodology presented has been tested against a large number of experimental states. The measurements have underlined the sensitivity of the MSA measured reactivities to core geometry changes and control rod perturbations; the efficiency of MSM factors to dramatically correct for this sensitivity is underlined, making of this technique a relevant methodology in view of the incoming US RACE program to be performed in TRIGA reactors

  9. The LBL [Lawrence Berkeley Laboratory] multiple beam experiments

    International Nuclear Information System (INIS)

    Fessenden, T.J.; Keefe, D.; Kim, C.; Meuth, H.; Warwick, A.

    1987-03-01

    The multiple-beam induction linac approach to a heavy ion driver for inertial confinement, fusion features continuous current amplification along the accelerator and a minimum of beam manipulations from source to pellet. Current amplification and bunch length control require careful shaping of the accelerating voltages. MBE-4 is designed as a four-beam induction linac that models much of the accelerator physics of the electrostatically focused section of a significantly longer induction accelerator. Four space-charge-dominated Cs + beams, initially about one meter in length at a current of 13 mA, are focused by electrostatic quadrupoles and accelerated in parallel from 200 to nearly 600 keV. The energy will reach approximately one MeV when the accelerator is complete. Experiments have proceeded in parallel with the construction of the apparatus which began in FY 85 and is now more than half complete. The results show a current amplification, so far, by a factor of 2.8 in good agreement with the longitudinal acceleration calculations

  10. A Preshower Photon Multiplicity Detector for the ALICE Experiment

    CERN Document Server

    Aggarwal, M M; Baba, P V K S; Badyal, S K; Bharti, A; Bhasin, A; Bhati, A K; Bhatia, V S; Chattopadhyay, S; Dubey, A K; Dutta-Majumdar, M R; Mazumdar, K; Ganti, M S; Ghosh, P; Sen-Gupta, A; Gupta, V K; Mahapatra, D P; Mangotra, L K; Mohanty, B; Nayak, T K; Phatak, S C; Raniwala, R; Raniwala, S; Rao, N K; Sambyal, S S; Singaraju, R N; Sinha, B; Trivedi, M D; Viyogi, Y P

    1999-01-01

    A preshower Photon Multiplicity Detector (PMD) is proposed to be implemented in the ALICE experiment to study event shapes and isospin fluctuations. The PMD, to be mounted on the magnet door at 6m from the vertex, has fine granularity and full azimuthal coverage in the pseudo-rapidity region 1.8

  11. Mechanisms of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplicon

    NARCIS (Netherlands)

    Eijdems, E. W.; de Haas, M.; Coco-Martin, J. M.; Ottenheim, C. P.; Zaman, G. J.; Dauwerse, H. G.; Breuning, M. H.; Twentyman, P. R.; Borst, P.; Baas, F.

    1995-01-01

    Some multidrug resistant cell lines over-express the gene encoding the multidrug-resistance-associated protein (MRP). In all cell lines reported thus far, over-expression is associated with gene amplification. We have studied the predominant mechanisms of MRP over-expression in 4 human lung-cancer

  12. School Nurse Resilience: Experiences after Multiple Natural Disasters

    Science.gov (United States)

    Broussard, Lisa; Myers, Rachel

    2010-01-01

    This qualitative descriptive study explored the experiences of school nurses in coastal Louisiana, who were affected by Hurricanes Gustav and Ike in 2008 and who had also been in the path of destruction caused by Hurricanes Katrina and Rita in 2005. The purpose of the study was to describe the experiences of school nurses affected by repeated…

  13. Estimation of caries experience by multiple imputation and direct standardization

    NARCIS (Netherlands)

    Schuller, A. A.; Van Buuren, S.

    2014-01-01

    Valid estimates of caries experience are needed to monitor oral population health. Obtaining such estimates in practice is often complicated by nonresponse and missing data. The goal of this study was to estimate caries experiences in a population of children aged 5 and 11 years, in the presence of

  14. Estimation of Caries Experience by Multiple Imputation and Direct Standardization

    NARCIS (Netherlands)

    Schuller, A. A.; van Buuren, S.

    2014-01-01

    Valid estimates of caries experience are needed to monitor oral population health. Obtaining such estimates in practice is often complicated by nonresponse and missing data. The goal of this study was to estimate caries experiences in a population of children aged 5 and 11 years, in the presence of

  15. Over-expression of Arabidopsis DnaJ (Hsp40) contributes to NaCl ...

    African Journals Online (AJOL)

    Over-expression of Arabidopsis DnaJ (Hsp40) contributes to NaCl-stress tolerance. Z Zhichang, Z Wanrong, Y Jinping, Z Jianjun, LZL Xufeng, Y Yang. Abstract. DnaJ (Hsp40), a heat shock protein, is a molecular chaperones responsive to various environmental stress. To analyze the protective role of DnaJ, we obtained ...

  16. Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase

    International Nuclear Information System (INIS)

    Brizio, Carmen; Galluccio, Michele; Wait, Robin; Torchetti, Enza Maria; Bafunno, Valeria; Accardi, Rosita; Gianazza, Elisabetta; Indiveri, Cesare; Barile, Maria

    2006-01-01

    FAD synthetase (FADS) (EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor FAD. Two hypothetical human FADSs, which are the products of FLAD1 gene, were over-expressed in Escherichia coli and identified by ESI-MS/MS. Isoform 1 was over-expressed as a T7-tagged protein which had a molecular mass of 63 kDa on SDS-PAGE. Isoform 2 was over-expressed as a 6-His-tagged fusion protein, carrying an extra 84 amino acids at the N-terminal with an apparent molecular mass of 60 kDa on SDS-PAGE. It was purified near to homogeneity from the soluble cell fraction by one-step affinity chromatography. Both isoforms possessed FADS activity and had a strict requirement for MgCl 2 , as demonstrated using both spectrophotometric and chromatographic methods. The purified recombinant isoform 2 showed a specific activity of 6.8 ± 1.3 nmol of FAD synthesized/min/mg protein and exhibited a K M value for FMN of 1.5 ± 0.3 μM. This is First report on characterization of human FADS, and First cloning and over-expression of FADS from an organism higher than yeast

  17. Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

    International Nuclear Information System (INIS)

    Flanagan, Louise; Whyte, Lorna; Chatterjee, Namita; Tenniswood, Martin

    2010-01-01

    Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s) of the secretory isoform in breast tumor progression and metastasis. To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells

  18. Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Chatterjee Namita

    2010-03-01

    Full Text Available Abstract Background Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s of the secretory isoform in breast tumor progression and metastasis. Methods To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. Results In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. Conclusions These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.

  19. Restoration of γ-ray multiplicity distributions from experiments with low efficiency multiplicity filters

    International Nuclear Information System (INIS)

    Bellia, G.; Del Zoppo, A.; Migneco, E.; Russo, G.; Istituto Nazionale di Fisica Nucleare, Catania

    1984-01-01

    The restoration of γ-ray multiplicity distributions from experimental p-fold coincidence distributions is discussed. It is shown that the restoration of the multiplicity from measurements with low total detection efficiency is an 'incorrectly posed problem'. While in the literature the analysis of the experimental data has been attempted only in terms of the lowest central moments of the multiplicity distribution, in this paper an unfolding method based on the minimization of the directioned discrepancies in the probability space is used. The method is found to work very well even if the total efficiency Ω <= 0.1. Realistic tests and a comparison with the usual method of analysis are presented. (orig.)

  20. The different effects of over-expressing murine NMDA receptor 2B subunit in the forebrain on conditioned taste aversion.

    Science.gov (United States)

    Li, Shijia; Gu, Yiran; Meng, Bo; Mei, Bing; Li, Fei

    2010-09-10

    The glutamate transmission system and the N-methyl-D-aspartate receptor (NMDA-R), in particular its 2B subunit (NR2B), have been reported to be possibly related to taste memory as a result of treatment with NMDA antagonists and agonists. In order to further study the role of the NR2B subunit in gustation memory, we applied four different taste aversive tasks to observe the behavior of a transgenic mice model in which the NR2B subunit was specifically over-expressed in the forebrain. We found that in both short- and long-term conditioned taste aversion (CTA) experiments, mice with forebrain expression of the NR2B transgene (Tg) showed significantly enhanced CTA 2 days after training. However, both the Tg and the wild-type (Wt) mice shared the same level of aversive memory on the 30th day after training. In both fast and slow extinction experiments, Tg mice maintained a higher CTA memory than that of control mice in most extinction trials. The third experiment, which involved testing the memory for familiar taste, demonstrated that NR2B augmentation had no benefit on the latent inhibition (LI) of CTA. In addition, the last experiment (two-taste LI) showed a suppression of enhanced CTA in Tg mice when the mice were exposed to both novel and familiar tastes. These data suggested that forebrain NR2B over-expression had different effects on gustatory learning and memory. The transgenic animals were only sensitive to novel but not familiar tastes, and up-regulation of NR2B resulted in enhanced CTA function for only a short period of time. 2010 Elsevier B.V. All rights reserved.

  1. Further experience with radiotherapy by multiple daily sessions

    Energy Technology Data Exchange (ETDEWEB)

    Svoboda, V H.J. [Saint Mary' s Hospital, Portsmouth (UK). Dept. of Radiotherapy and Oncology

    1978-05-01

    Since 1972 over 100 patients have been treated by frequent daily sessions of radiotherapy with a short overall time. Cobalt 60 teletherapy and 250 kV X-ray beams have been used with radical or palliative dosage. The tolerance to these regimes of the skin, breast, chest wall, neck, lung and pelvis is discussed and the tumour responses described. Radiotherapy by multiple daily sessions is clinically possible and often an advantage. Its therapeutic ratio is not inferior to comparable regimes using longer intervals.

  2. Higher Order Multiple Births in Nigeria: Experiences, Challenges ...

    African Journals Online (AJOL)

    women in Nigeria,[10] ... of three or more babies in one pregnancy. ... Objectives: The aim of this study is to describe the experience and outcome ... and build upon the work non-commercially, as long as the author is credited and the new ..... trend of women pursuing careers earlier in life and .... Achebe C. Things Fall Apart.

  3. Multiple blowdown pipe experiments with the PPOOLEX facility

    International Nuclear Information System (INIS)

    Puustinen, M.; Laine, J.; Raesaenen, A.

    2011-03-01

    This report summarizes the results of the experiments with two steel blowdown pipes carried out with the scaled down PPOOLEX test facility designed and constructed at Lappeenranta University of Technology. Steam was blown into the dry well compartment and from there through the blowdown pipes to the condensation pool. The main purpose of the experiment series was to study chugging phenomena (rapid condensation) while steam is discharged through two parallel blowdown pipes into the condensation pool filled with sub-cooled water. Particularly, the aim was to study if the pipe material (polycarbonate) used in the earlier experiment series with two blowdown pipes has had an effect on the general chugging behaviour and measured loads. In the experiments the initial temperature of the pool water was 20 deg. C. The steam flow rate ranged from 220 g/s to 2 350 g/s and the temperature of incoming steam from 148 deg. C to 207 deg. C. The formation and collapse of steam bubbles and the movement of the steam/water interface inside the pipes was non-synchronous. There could be even a 70 ms time difference between the occurrences of steam bubble collapses at the outlets of the two pipes. There was no clear pattern in which pipe the steam bubble first starts to collapse. Several successive bubbles could collapse first in either pipe but then the order changed for a single or several cycles. High pressure loads were measured inside the blowdown pipes due to rapid condensation of the steam volumes in the pipes and resulting water hammer effects. The loads seemed to be higher in pipe 1 than in pipe 2. An explanation for this could be a possible unequal distribution of steam flow between the two pipes. The pipe material has an effect on the condensation phenomena inside the blowdown pipes. A huge difference in the measured pressure curves inside the pipes could be observed compared to the experiments with the polycarbonate pipes. With the same test conditions the amplitude of the

  4. Multiple blowdown pipe experiments with the PPOOLEX facility

    Energy Technology Data Exchange (ETDEWEB)

    Puustinen, M.; Laine, J.; Raesaenen, A. (Lappeenranta Univ. of Technology, Nuclear Safety Research Unit (Finland))

    2011-03-15

    This report summarizes the results of the experiments with two steel blowdown pipes carried out with the scaled down PPOOLEX test facility designed and constructed at Lappeenranta University of Technology. Steam was blown into the dry well compartment and from there through the blowdown pipes to the condensation pool. The main purpose of the experiment series was to study chugging phenomena (rapid condensation) while steam is discharged through two parallel blowdown pipes into the condensation pool filled with sub-cooled water. Particularly, the aim was to study if the pipe material (polycarbonate) used in the earlier experiment series with two blowdown pipes has had an effect on the general chugging behaviour and measured loads. In the experiments the initial temperature of the pool water was 20 deg. C. The steam flow rate ranged from 220 g/s to 2 350 g/s and the temperature of incoming steam from 148 deg. C to 207 deg. C. The formation and collapse of steam bubbles and the movement of the steam/water interface inside the pipes was non-synchronous. There could be even a 70 ms time difference between the occurrences of steam bubble collapses at the outlets of the two pipes. There was no clear pattern in which pipe the steam bubble first starts to collapse. Several successive bubbles could collapse first in either pipe but then the order changed for a single or several cycles. High pressure loads were measured inside the blowdown pipes due to rapid condensation of the steam volumes in the pipes and resulting water hammer effects. The loads seemed to be higher in pipe 1 than in pipe 2. An explanation for this could be a possible unequal distribution of steam flow between the two pipes. The pipe material has an effect on the condensation phenomena inside the blowdown pipes. A huge difference in the measured pressure curves inside the pipes could be observed compared to the experiments with the polycarbonate pipes. With the same test conditions the amplitude of the

  5. Over-expressed maltose transporters in laboratory and lager yeasts: localization and competition with endogenous transporters.

    Science.gov (United States)

    Vidgren, Virve; Londesborough, John

    2018-05-31

    Plain and fluorescently tagged versions of Agt1, Mtt1 and Malx1 maltose transporters were over-expressed in two laboratory yeasts and one lager yeast. The plain and tagged versions of each transporter supported similar transport activities, indicating that they are similarly trafficked and have similar catalytic activities. When they were expressed under the control of the strong constitutive PGK1 promoter only minor proportions of the fluorescent transporters were associated with the plasma membrane, the rest being found in intracellular structures. Transport activity of each tagged transporter in each host was roughly proportional to the plasma membrane-associated fluorescence. All three transporters were subject to glucose-triggered inactivation when the medium glucose concentration was abruptly raised. Results also suggest competition between endogenous and over-expressed transporters for access to the plasma membrane. This article is protected by copyright. All rights reserved.

  6. Reduced seed germination in Arabidopsis over-expressing SWI/SNF2 ATPase genes.

    Science.gov (United States)

    Leeggangers, Hendrika A C F; Folta, Adam; Muras, Aleksandra; Nap, Jan-Peter; Mlynarova, Ludmila

    2015-02-01

    In the life of flowering plants, seed germination is a critical step to ensure survival into the next generation. Generally the seed prior to germination has been in a dormant state with a low rate of metabolism. In the transition from a dormant seed to a germinating seed, various epigenetic mechanisms play a regulatory role. Here, we demonstrate that the over-expression of chromatin remodeling ATPase genes (AtCHR12 or AtCHR23) reduced the frequency of seed germination in Arabidopsis thaliana up to 30% relative to the wild-type seeds. On the other hand, single loss-of-function mutations of the two genes did not affect seed germination. The reduction of germination in over-expressing mutants was more pronounced in stress conditions (salt or high temperature), showing the impact of the environment. Reduced germinations upon over-expression coincided with increased transcript levels of seed maturation genes and with reduced degradation of their mRNAs stored in dry seeds. Our results indicate that repression of AtCHR12/23 gene expression in germinating wild-type Arabidopsis seeds is required for full germination. This establishes a functional link between chromatin modifiers and regulatory networks towards seed maturation and germination. © 2014 Scandinavian Plant Physiology Society.

  7. Induction of epigenetic variation in Arabidopsis by over-expression of DNA METHYLTRANSFERASE1 (MET1.

    Directory of Open Access Journals (Sweden)

    Samuel Brocklehurst

    Full Text Available Epigenetic marks such as DNA methylation and histone modification can vary among plant accessions creating epi-alleles with different levels of expression competence. Mutations in epigenetic pathway functions are powerful tools to induce epigenetic variation. As an alternative approach, we investigated the potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1 (MET1 for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance of cytosine methylation at symmetrical CG positions. At some loci, which contain dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss of all cytosines methylation marks. We find that over-expression of both catalytically active and inactive versions of MET1 stochastically generates new epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins, which results for most loci in an increase in expression. Individual transformants share some common phenotypes and genes with altered gene expression. Altered expression states can be transmitted to the next generation, which does not require the continuous presence of the MET1 transgene. Long-term stability and epigenetic features differ for individual loci. Our data show that over-expression of MET1, and potentially of other genes encoding epigenetic factors, offers an alternative strategy to identify epigenetic target genes and to create novel epi-alleles.

  8. Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

    Science.gov (United States)

    Lorente Fernández, L; Monte Boquet, E; Pérez-Miralles, F; Gil Gómez, I; Escutia Roig, M; Boscá Blasco, I; Poveda Andrés, J L; Casanova-Estruch, B

    2014-06-01

    Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor's analysis and overall impression. Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%). Treatment was discontinued in 16 patients because of ineffectiveness (7 patients), withdrawal (4), and adverse effects (5). The median exposure time in patients whose treatment was discontinued was 30 days vs 174 days in those whose treatment continued at the end of the study. THC/CBD was effective in 80% of patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1), nausea (1), and paranoid ideation (1). THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  9. Students' integration of multiple representations in a titration experiment

    Science.gov (United States)

    Kunze, Nicole M.

    A complete understanding of a chemical concept is dependent upon a student's ability to understand the microscopic or particulate nature of the phenomenon and integrate the microscopic, symbolic, and macroscopic representations of the phenomenon. Acid-base chemistry is a general chemistry topic requiring students to understand the topics of chemical reactions, solutions, and equilibrium presented earlier in the course. In this study, twenty-five student volunteers from a second semester general chemistry course completed two interviews. The first interview was completed prior to any classroom instruction on acids and bases. The second interview took place after classroom instruction, a prelab activity consisting of a titration calculation worksheet, a titration computer simulation, or a microscopic level animation of a titration, and two microcomputer-based laboratory (MBL) titration experiments. During the interviews, participants were asked to define and describe acid-base concepts and in the second interview they also drew the microscopic representations of four stages in an acid-base titration. An analysis of the data showed that participants had integrated the three representations of an acid-base titration to varying degrees. While some participants showed complete understanding of acids, bases, titrations, and solution chemistry, other participants showed several alternative conceptions concerning strong acid and base dissociation, the formation of titration products, and the dissociation of soluble salts. Before instruction, participants' definitions of acid, base, and pH were brief and consisted of descriptive terms. After instruction, the definitions were more scientific and reflected the definitions presented during classroom instruction.

  10. Multiple Pyogenic Abscess of the Hybrid Mice on the Course of Radiation Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Heon; Shin, Sei One; Kim, Myung Se; Choi, Won Hee; Kim, Seung Hoon [Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    1985-12-15

    Even though the mechanism and the nature of radiation induced pneumonitis, esophagitis and gastroenteritis were detailed by many authors, complicated secondary infection is still serious problem, sometimes fatal, even today. We experience a case of multiple pyogenic abscess in subcutaneous tissue of the back and both kidneys which could not differentiate from multiple metastatic sarcoma grossly, and report with review of literatures, lab. findings.

  11. Perspective and Experiences of Iranian People With Multiple Sclerosis Regarding Leisure: A Qualitative Study

    OpenAIRE

    Ghanbari; Shayanpour

    2015-01-01

    Background Multiple Sclerosis, as a progressive disease, influences most of occupational performance areas. Objectives This study was conducted to describe the perspectives and experiences regarding leisure of people with multiple sclerosis in Ahvaz city, Iran. Patients and Methods The study was a descriptive phenomenological study using purposeful sampling. Data saturation was ach...

  12. YUCCA6 over-expression demonstrates auxin function in delaying leaf senescence in Arabidopsis thaliana

    KAUST Repository

    Kim, Jeong Im

    2011-04-21

    The Arabidopsis thaliana YUCCA family of flavin monooxygenase proteins catalyses a rate-limiting step in de novo auxin biosynthesis. A YUCCA6 activation mutant, yuc6-1D, has been shown to contain an elevated free IAA level and to display typical high-auxin phenotypes. It is reported here that Arabidopsis plants over-expressing YUCCA6, such as the yuc6-1D activation mutant and 35S:YUC6 transgenic plants, displayed dramatic longevity. In addition, plants over-expressing YUCCA6 exhibited classical, delayed dark-induced and hormone-induced senescence in assays using detached rosette leaves. However, plants over-expressing an allele of YUCCA6, that carries mutations in the NADPH cofactor binding site, exhibited neither delayed leaf senescence phenotypes nor phenotypes typical of auxin overproduction. When the level of free IAA was reduced in yuc6-1D by conjugation to lysine, yuc6-1D leaves senesced at a rate similar to the wild-type leaves. Dark-induced senescence in detached leaves was accompanied by a decrease in their free IAA content, by the reduced expression of auxin biosynthesis enzymes such as YUCCA1 and YUCCA6 that increase cellular free IAA levels, and by the increased expression of auxin-conjugating enzymes encoded by the GH3 genes that reduce the cellular free auxin levels. Reduced transcript abundances of SAG12, NAC1, and NAC6 during senescence in yuc6-1D compared with the wild type suggested that auxin delays senescence by directly or indirectly regulating the expression of senescence-associated genes. 2011 The Author(s).

  13. [Over-expression of BDNF inhibits angiotensin II-induced apoptosis of cardiomyocytes in SD rats].

    Science.gov (United States)

    Cao, Jingli; Wu, Yingfeng; Liu, Geming; Li, Zhenlong

    2018-03-01

    Objective To investigate the role and molecular mechanism of brain-derived neurotrophic factor (BDNF) against the process of cardiomyocyte hypertrophy and apoptosis. Methods Cardiomyocyte hypertrophy were estabolished by angiotensin II (Ang II) in neonatal cardiomyocytes in vitro and incomplete ligature of abdominal aorta of SD rats in vivo. BDNF over-expressing recombinant vector pcDNA5-BDNF was transfected into cardiomyocytes by liposomes. Immunofluorescence staining was used to detect the effect of BDNF transfection on the surface area of myocardial cells. The effect of BDNF transfection on the apoptosis of cardiomyocytes was assayed by flow cytometry. Real-time fluorescent quantitative PCR was performed to detect the effect of over-expression of BDNF on the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs in cardiomyocytes. Western blot assay was used to observe the changes of BDNF, ANP and BNP, calmodulin kinase 2 (CaMK2) and phosphorylated calmodulin kinase 2 (p-CaMK2), calcineurin (CaN), p-CaN, nuclear factor of activated T cells 3 (NFATC3) and p-NFATC3 protein expressions in the myocardial tissues and cardiomyocytes. Results The expression of BDNF protein increased significantly in cardiac hypertrophy animal and cell models in a time-dependent manner. Compared with the untransfected control cardiomyocytes, the surface area of cardiomyocytes, the rate of apoptosis, the levels of ANP and BNP mRNA and protein expression, the levels of p-CaMK2 and CaN protein in the BDNF over-expressed cardiomyocytes were remarkably reduced, while the level of p-NFATC3 protein rose significantly. Conclusion BDNF inhibits the apoptosis of cardiomyocytes induced by Ang II, and it plays the role by inhibiting CaMK2 and CaN signaling pathways.

  14. Reactive astrocytes over express TSPO and are detected by TSPO Positron Emission Tomography Imaging

    International Nuclear Information System (INIS)

    Lavisse, Sonia; Guillermier, Martine; Herard, Anne-Sophie; Petit, Fanny; Delahaye, Marion; Van Camp, Nadja; Ben Haim, Lucile; Lebon, Vincent; Delzescaux, Thierry; Bonvento, Gilles; Hantraye, Philippe; Escartin, Carole; Remy, Philippe; Dolle, Frederic

    2012-01-01

    Astrocytes and micro-glia become reactive under most brain pathological conditions, making this neuro-inflammation process a surrogate marker of neuronal dysfunction. Neuro-inflammation is associated with increased levels of translocator protein 18kDa(TSPO) and binding sites for TSPO ligands. Positron emission tomography (PET) imaging of TSPO is thus commonly used to monitor neuro-inflammation in preclinical and clinical studies. It is widely considered that TSPO PET signal reveals reactive micro-glia, although a few studies suggested a potential contribution of reactive astrocytes. Because astrocytes and micro-glia play very different roles, it is crucial to determine whether reactive astrocytes can also over-express TSPO and yield to a detectable TSPO PET signal in vivo. We used a model of selective astrocyte activation through lentiviral gene transfer of the cytokine ciliary neuro-trophic factor (CNTF) into the rat striatum, in the absence of neuro-degeneration. CNTF induced an extensive activation of astrocytes, which over-expressed GFAP and become hypertrophic, whereas micro-glia displayed minimal increase in reactive markers.Two TSPO radioligands, [ 18 F]DPA-714[N,N-diethyl-2-(2-(4-(2-[ 18 F]fluoroethoxy)phenyl) - 5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide] and [ 11 C]SSR180575 (7-chloro-N,N-dimethyl-5-[ 11 C]methyl-4-oxo-3-phenyl - 3,5-dihydro-4H-pyridazino[4,5- b]indole-1-acetamide),showed a significant binding in the lenti-CNTF-injected striatum that was saturated and displaced by PK11195[N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-isoquinoline-3-carboxamide]. The volume of radioligand binding matched the GFAP immuno-positive volume. TSPO mRNA levels were significantly increased, and TSPO protein was over-expressed by CNTF-activated astrocytes. We show that reactive astrocytes over-express TSPO, yielding to a significant and selective binding of TSPO radioligands. Therefore, caution must be used when interpreting TSPO PET imaging in animals or

  15. Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

    Science.gov (United States)

    Lewis, Jo E; Brameld, John M; Hill, Phil; Cocco, Cristina; Noli, Barbara; Ferri, Gian-Luca; Barrett, Perry; Ebling, Francis J P; Jethwa, Preeti H

    2017-01-01

    VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well

  16. Theoretical investigations of quantum correlations in NMR multiple-pulse spin-locking experiments

    Science.gov (United States)

    Gerasev, S. A.; Fedorova, A. V.; Fel'dman, E. B.; Kuznetsova, E. I.

    2018-04-01

    Quantum correlations are investigated theoretically in a two-spin system with the dipole-dipole interactions in the NMR multiple-pulse spin-locking experiments. We consider two schemes of the multiple-pulse spin-locking. The first scheme consists of π /2-pulses only and the delays between the pulses can differ. The second scheme contains φ-pulses (0Quantum discord is obtained for the first scheme of the multiple-pulse spin-locking experiment at different temperatures.

  17. Charged particle multiplicity distributions in e+e--annihilation processes in the LEP experiments

    International Nuclear Information System (INIS)

    Shlyapnikov, P.V.

    1992-01-01

    Results of studies of the charged particle multiplicity distributions in the process of e + e - -annihilation into hadrons obtained in experiments at LEP accelerator in CERN are reviewed. Universality in energy dependence of the average charged particle multiplicity in e + e - and p ± p collisions, evidence for KNO-scaling in e + e - data, structure in multiplicity distribution and its relation to the jet structure of events, average particle multiplicities or quark and gluon jets, 'clan' picture and other topics are discussed. 73 refs.; 20 figs.; 3 tabs

  18. Multiple Intelligences, Motivations and Learning Experience Regarding Video-Assisted Subjects in a Rural University

    Science.gov (United States)

    Hajhashemi, Karim; Caltabiano, Nerina; Anderson, Neil; Tabibzadeh, Seyed Asadollah

    2018-01-01

    This study investigates multiple intelligences in relation to online video experiences, age, gender, and mode of learning from a rural Australian university. The inter-relationships between learners' different intelligences and their motivations and learning experience with the supplementary online videos utilised in their subjects are…

  19. Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Good

    2010-09-01

    Full Text Available The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

  20. Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Anna Velia Stazi

    2010-12-01

    Full Text Available In celiac disease (CD, for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines and exogenous (environment, nutritional deficiency factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15 is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.

  1. VCC-1 over-expression inhibits cisplatin-induced apoptosis in HepG2 cells

    International Nuclear Information System (INIS)

    Zhou, Zhitao; Lu, Xiao; Zhu, Ping; Zhu, Wei; Mu, Xia; Qu, Rongmei; Li, Ming

    2012-01-01

    Highlights: ► VCC-1 is hypothesized to be associated with carcinogenesis. ► Levels of VCC-1 are increased significantly in HCC. ► Over-expression of VCC-1 could promotes cellular proliferation rate. ► Over-expression of VCC-1 inhibit the cisplatin-provoked apoptosis in HepG2 cells. ► VCC-1 plays an important role in control the tumor growth and apoptosis. -- Abstract: Vascular endothelial growth factor-correlated chemokine 1 (VCC-1), a recently described chemokine, is hypothesized to be associated with carcinogenesis. However, the molecular mechanisms by which aberrant VCC-1 expression determines poor outcomes of cancers are unknown. In this study, we found that VCC-1 was highly expressed in hepatocellular carcinoma (HCC) tissue. It was also associated with proliferation of HepG2 cells, and inhibition of cisplatin-induced apoptosis of HepG2 cells. Conversely, down-regulation of VCC-1 in HepG2 cells increased cisplatin-induced apoptosis of HepG2 cells. In summary, these results suggest that VCC-1 is involved in cisplatin-induced apoptosis of HepG2 cells, and also provides some evidence for VCC-1 as a potential cellular target for chemotherapy.

  2. Widespread Over-Expression of the X Chromosome in Sterile F1 Hybrid Mice

    Science.gov (United States)

    Good, Jeffrey M.; Giger, Thomas; Dean, Matthew D.; Nachman, Michael W.

    2010-01-01

    The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F1 males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F1 hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility. PMID:20941395

  3. Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

    Science.gov (United States)

    Good, Jeffrey M; Giger, Thomas; Dean, Matthew D; Nachman, Michael W

    2010-09-30

    The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

  4. OVER-EXPRESSION OF GENE ENCODING FATTY ACID METABOLIC ENZYMES IN FISH

    Directory of Open Access Journals (Sweden)

    Alimuddin Alimuddin

    2008-12-01

    Full Text Available Eicosapentaenoic acid (EPA, 20:5n-3 and docosahexaenoic acid (DHA, 22:6n-3 have important nutritional benefits in humans. EPA and DHA are mainly derived from fish, but the decline in the stocks of major marine capture fishes could result in these fatty acids being consumed less. Farmed fish could serve as promising sources of EPA and DHA, but they need these fatty acids in their diets. Generation of fish strains that are capable of synthesizing enough amounts of EPA/DHA from the conversion of α-linolenic acid (LNA, 18:3n-3 rich oils can supply a new EPA/DHA source. This may be achieved by over-expression of genes encoding enzymes involved in HUFA biosynthesis. In aquaculture, the successful of this technique would open the possibility to reduce the enrichment of live food with fish oils for marine fish larvae, and to completely substitute fish oils with plant oils without reducing the quality of flesh in terms of EPA and DHA contents. Here, three genes, i.e. Δ6-desaturase-like (OmΔ6FAD, Δ5-desaturase-like (OmΔ5FAD and elongase-like (MELO encoding EPA/DHA metabolic enzymes derived from masu salmon (Oncorhynchus masou were individually transferred into zebrafish (Danio rerio as a model to increase its ability for synthesizing EPA and DHA. Fatty acid analysis showed that EPA content in whole body of the second transgenic fish generation over-expressing OmΔ6FAD gene was 1.4 fold and that of DHA was 2.1 fold higher (P<0.05 than those in non-transgenic fish. The EPA content in whole body of transgenic fish over-expressing OmΔ5FAD gene was 1.21-fold, and that of DHA was 1.24-fold higher (P<0.05 than those in nontransgenic fish. The same patterns were obtained in transgenic fish over-expressing MELO gene. EPA content was increased by 1.30-fold and DHA content by 1.33-fold higher (P<0.05 than those in non-transgenic fish. The results of studies demonstrated that fatty acid content of fish can be enhanced by over-expressing

  5. Strengthening Triterpene Saponins Biosynthesis by Over-Expression of Farnesyl Pyrophosphate Synthase Gene and RNA Interference of Cycloartenol Synthase Gene in Panax notoginseng Cells

    Directory of Open Access Journals (Sweden)

    Yan Yang

    2017-04-01

    Full Text Available To conform to the multiple regulations of triterpene biosynthesis, the gene encoding farnesyl pyrophosphate synthase (FPS was transformed into Panax notoginseng (P. notoginseng cells in which RNA interference (RNAi of the cycloartenol synthase (CAS gene had been accomplished. Transgenic cell lines showed both higher expression levels of FPS and lower expression levels of CAS compared to the wild-type (WT cells. In the triterpene and phytosterol analysis, transgenic cell lines provided a higher accumulation of total triterpene saponins, and a lower amount of phytosterols in comparison with the WT cells. Compared with the cells in which RNAi of the CAS gene was achieved, the cells with simultaneously over-expressed FPS and silenced CAS showed higher triterpene contents. These results demonstrate that over-expression of FPS can break the rate-limiting reaction catalyzed by FPS in the triterpene saponins biosynthetic pathway; and inhibition of CAS expression can decrease the synthesis metabolic flux of the phytosterol branch. Thus, more precursors flow in the direction of triterpene synthesis, and ultimately promote the accumulation of P. notoginseng saponins. Meanwhile, silencing and over-expressing key enzyme genes simultaneously is more effective than just manipulating one gene in the regulation of saponin biosynthesis.

  6. Multiple victimization experiences of urban elementary school students: associations with psychosocial functioning and academic performance.

    Science.gov (United States)

    Holt, Melissa K; Finkelhor, David; Kantor, Glenda Kaufman

    2007-05-01

    This study explored the victimization experiences of urban elementary school students to determine whether subsets of youth emerged with similar victimization profiles (e.g., no victimization, multiple types of victimization). It also evaluated whether multiple victimization was associated with greater psychological distress and lower academic performance. Participants were 689 fifth grade students from an urban, ethnically diverse school district in the Northeast. Youth completed self-report measures in school about bullying victimization, victimization in the home and community, and psychosocial functioning. Cluster analysis suggested the existence of three distinct youth profiles: those with minimal victimization, those victimized primarily by their peers, and those with multiple types of victimizations. As hypothesized, youth with multiple victimizations experienced more psychological distress and earned lower grades than their peers. Findings highlight the heterogeneity of youth victimization experiences and their relations to functioning, and have implications for treatment planning among practitioners working with youth.

  7. DEK over expression as an independent biomarker for poor prognosis in colorectal cancer

    International Nuclear Information System (INIS)

    Lin, Lijuan; Piao, Junjie; Gao, Wenbin; Piao, Yingshi; Jin, Guang; Ma, Yue; Li, Jinzi; Lin, Zhenhua

    2013-01-01

    The DEK protein is related to chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. High expression levels of the human DEK gene have been correlated with numerous human malignancies. This study explores the roles of DEK in tumor progression and as a prognostic determinant of colorectal cancer. Colorectal cancer specimens from 109 patients with strict follow-up, and colorectal adenomas from 52 patients were selected for analysis of DEK protein by immunohistochemistry. The correlations between DEK over expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher’s exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. DEK protein showed a nuclear immunohistochemical staining pattern in colorectal cancers. The strongly positive rate of DEK protein was 48.62% (53/109) in colorectal cancers, which was significantly higher than that in either adjacent normal colon mucosa (9.17%, 10/109) or colorectal adenomas (13.46%, 7/52). DEK over expression in colorectal cancers was positively correlated with tumor size, grade, lymph node metastasis, serosal invasion, late stage, and disease-free survival- and 5-year survival rates. Further analysis showed that patients with late stage colorectal cancer and high DEK expression had worse survival rates than those with low DEK expression. Moreover, multivariate analysis showed high DEK expression, serosal invasion, and late stage are significant independent risk factors for mortality in colorectal cancer. DEK plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor of colorectal cancers

  8. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    Science.gov (United States)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-08-06

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed.

  9. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    International Nuclear Information System (INIS)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed

  10. Over-expression of miR158 causes pollen abortion in Brassica campestris ssp. chinensis.

    Science.gov (United States)

    Ma, Zhiming; Jiang, Jianxia; Hu, Ziwei; Lyu, Tianqi; Yang, Yang; Jiang, Jingjing; Cao, Jiashu

    2017-02-01

    We identified and cloned the two precursors of miR158 and its target gene in Brassica campestris ssp. chinensis, which both had high relative expression in the inflorescences. Further study revealed that over-expression of miR158 caused reduced pollen varbility, which was caused by the degradation of pollen contents from the binucleate microspore stage. These results first suggest the role of miR158 in pollen development of Brassica campestris ssp. chinensis. MicroRNAs (miRNAs) play crucial roles in many important growth and development processes both in plants and animals by regulating the expression of their target genes via mRNA cleavage or translational repression. In this study, miR158, a Brassicaceae specific miRNA, was functionally characterized with regard to its role in pollen development of non-heading Chinese cabbage (Brassica campestris ssp. chinensis). Two family members of miR158 in B. campestris, namely bra-miR158a1 and bra-miR158a2, and their target gene bra027656, which encodes a pentatricopeptide repeat (PPR) containing protein, were identified. Then, qRT-PCR analysis and GUS-reporter system revealed that both bra-miR158 and its target gene had relatively high expression levels in the inflorescences. Further study revealed that over-expression of miR158 caused reduced pollen varbility and pollen germination ratio, and the degradation of pollen contents from the binucleate microspore stage was also found in those deformed pollen grains, which led to pollen shrinking and collapse in later pollen development stage. These results first shed light on the importance of miR158 in pollen development of Brassica campestris ssp. chinensis.

  11. Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration

    International Nuclear Information System (INIS)

    Zampol, Mariana A.; Busso, Cleverson; Gomes, Fernando; Ferreira-Junior, Jose Ribamar; Tzagoloff, Alexander; Barros, Mario H.

    2010-01-01

    Research highlights: → COQ10 deletion elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q 2 , a synthetic diffusible ubiquinone. → The significance that purified Coq10p contains bound Q 6 was examined by testing over-expression of Coq10p on respiration. → Inhibition of CoQ function due to Coq10p excess strength our hypothesis of Coq10p function in CoQ delivery. → Respiratory deficiency caused by more Coq10p was specific and restored by Q 2 in mitochondria or by Coq8p in cells. → Coq8p over-production on other coq mutants revealed a surprisingly higher stability of other Coq proteins. -- Abstract: COQ10 deletion in Saccharomyces cerevisiae elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q 2 . Rescue of respiration by Q 2 is a characteristic of mutants blocked in coenzyme Q 6 synthesis. Unlike Q 6 deficient mutants, mitochondria of the coq10 null mutant have wild-type concentrations of Q 6 . The physiological significance of earlier observations that purified Coq10p contains bound Q 6 was examined in the present study by testing the in vivo effect of over-expression of Coq10p on respiration. Mitochondria with elevated levels of Coq10p display reduced respiration in the bc1 span of the electron transport chain, which can be restored with exogenous Q 2 . This suggests that in vivo binding of Q 6 by excess Coq10p reduces the pool of this redox carrier available for its normal function in providing electrons to the bc1 complex. This is confirmed by observing that extra Coq8p relieves the inhibitory effect of excess Coq10p. Coq8p is a putative kinase, and a high-copy suppressor of the coq10 null mutant. As shown here, when over-produced in coq mutants, Coq8p counteracts turnover of Coq3p and Coq4p subunits of the Q-biosynthetic complex. This can account for the observed rescue by COQ8 of the respiratory defect in strains over-producing Coq10p.

  12. Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration

    Energy Technology Data Exchange (ETDEWEB)

    Zampol, Mariana A.; Busso, Cleverson; Gomes, Fernando [Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo (Brazil); Ferreira-Junior, Jose Ribamar [Escola de Artes, Ciencias e Humanidades, Universidade de Sao Paulo, Sao Paulo (Brazil); Tzagoloff, Alexander [Department of Biological Sciences, Columbia University, NY (United States); Barros, Mario H., E-mail: mariohb@usp.br [Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo (Brazil)

    2010-11-05

    Research highlights: {yields} COQ10 deletion elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q{sub 2}, a synthetic diffusible ubiquinone. {yields} The significance that purified Coq10p contains bound Q{sub 6} was examined by testing over-expression of Coq10p on respiration. {yields} Inhibition of CoQ function due to Coq10p excess strength our hypothesis of Coq10p function in CoQ delivery. {yields} Respiratory deficiency caused by more Coq10p was specific and restored by Q{sub 2} in mitochondria or by Coq8p in cells. {yields} Coq8p over-production on other coq mutants revealed a surprisingly higher stability of other Coq proteins. -- Abstract: COQ10 deletion in Saccharomyces cerevisiae elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q{sub 2}. Rescue of respiration by Q{sub 2} is a characteristic of mutants blocked in coenzyme Q{sub 6} synthesis. Unlike Q{sub 6} deficient mutants, mitochondria of the coq10 null mutant have wild-type concentrations of Q{sub 6}. The physiological significance of earlier observations that purified Coq10p contains bound Q{sub 6} was examined in the present study by testing the in vivo effect of over-expression of Coq10p on respiration. Mitochondria with elevated levels of Coq10p display reduced respiration in the bc1 span of the electron transport chain, which can be restored with exogenous Q{sub 2}. This suggests that in vivo binding of Q{sub 6} by excess Coq10p reduces the pool of this redox carrier available for its normal function in providing electrons to the bc1 complex. This is confirmed by observing that extra Coq8p relieves the inhibitory effect of excess Coq10p. Coq8p is a putative kinase, and a high-copy suppressor of the coq10 null mutant. As shown here, when over-produced in coq mutants, Coq8p counteracts turnover of Coq3p and Coq4p subunits of the Q-biosynthetic complex. This can account for the observed rescue by COQ8 of the respiratory defect in strains

  13. Children with Multiple Stays at Refuges for Abused Women and Their Experiences of Teacher Recognition

    Science.gov (United States)

    Selvik, Sabreen; Raaheim, Arild; Øverlien, Carolina

    2017-01-01

    Numerous children around the world are forced to make multiple moves with their mothers in and out of refuges for abused women. Each time, they experience a sudden upheaval of their familiar environment. For these children, domestic violence and flight from violence is not an isolated event but part of their upbringing. Few statistics and little…

  14. Leaders' Experiences with High School-College Writing Center Collaborations: A Qualitative Multiple-Case Study

    Science.gov (United States)

    Story, Julie A.

    2014-01-01

    The purpose of this qualitative multiple-case study was to explore academic leaders' experiences with the organizational elements of their own high school-college writing center collaborations. Conjoining theories framed this study: collaborative leadership theory, Kenneth Bruffee's notion of social constructionism and collaborative learning…

  15. Neutron reflection effect on total absorption detector method used in SWINPC neutron multiplication experiment for beryllium

    International Nuclear Information System (INIS)

    Tian Dongfeng; Ho Yukun; Yang Fujia

    2001-01-01

    The SWINPC integral experiment on neutron multiplication in bulk beryllium showed that there were marked discrepancies between experimental data and calculated values with the ENDF/B-VI data. The calculated values become higher than experimental ones as the sample thickness increases. Several works had been devoted to find problems existing in the experiment. This paper discusses the neutron reflection effect on the total absorption detector method which was used in the experiment to measure the neutron leakage from samples. One systematic correction is suggested to make the experimental values agree with the calculated ones with the ENDF/B-VI data within experimental errors. (author)

  16. Investigating the effect of multiple layers of insulation with a bubble wrap experiment

    Science.gov (United States)

    Eggers, Dolores; Ruiz, Michael J.

    2018-03-01

    We provide a fun, inexpensive laboratory experiment for students to investigate the effects of multiple layers of insulation and observe diminishing values for additional layers using bubble wrap. This experiment provides an opportunity for students to learn about heat transfer through conduction using readily available materials. A water-ice pack is placed on top of five layers of bubble wrap. The temperature is taken between each layer periodically for at least 15 min. Students determine asymptotic temperatures for varying layers. This experiment also suggests a real world application.

  17. GPX4 and GPX7 Over-Expression in Human Hepatocellular Carcinoma Tissues

    Science.gov (United States)

    Guerriero, E.; Capone, F.; Accardo, M.; Sorice, A.; Costantini, M.; Colonna, G.; Castello, G.

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. The selenium is an essential trace mineral implicated as a key factor in the early stage of cancer and exerts its biological function through the selenoproteins. In the last years our group has been studying the involvement of some selenoproteins in HCC. However, no many data are reported in literature about the correlation between HCC and the glutathione peroxidases (GPXs), both selenium and non selenium-containing GPXs. In this paper we have evaluated the GPX4 and GPX7 expression in some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV)-related cirrhosis and HCC by immunohistochemistry and RT-qPCR analysis. Our results evidenced that i) GPX4 and GPX7 had a statistically significant over-expression in HCC tissues compared to cirrhotic counterparts used as non tumor tissues, and ii) their expression was higher in grade III HCC tissues with respect to grade I-II samples. Therefore, we propose to use GPX4 and GPX7 as possible markers for improving HCC diagnosis/prognosis. PMID:26708178

  18. Over-expression of Gene FaASR Promotes Strawberry Fruit Coloring

    Directory of Open Access Journals (Sweden)

    Liu Zhongjie

    2015-11-01

    Full Text Available Fruit development and ripening is a complicate process. Although much progress has been made on the ripenig process, the molecular mechamism of fruit development is not yet clear. In this study, we used ‘Sweet Charlie’ strawberry as test materials, based on cloning the strawberries ASR homologous gene, we carried out the bioinformatics and temporal expression analysis of FaASR, by manipulating ASR gene expression level in strawberry fruit, we tested the changes of physiological indicators, including sugar, ABA, pigments content, and fruit firmness, as well as phenotypic changes. In addition, we measured the expression changes of some anthocyanin-related gene, such as CHS and UFGT, by which we revealed the regulation mechanisms of ASR gene over strawberry fruit ripening. Strawberry ASR contained a typical domain of ABA/WDS that was related to fruit ripening and stress-resistance, and ASR gene over-expression could promote strawberry fruit coloring, endogenous ABA and sucrose accumulation, fruit softening, and induced the transcription levels of anthocyanin-related genes CHS and UFGT. The present study will further reveal the molecular mechanisms of information transmission in fruit development, and will also play an important foundation for future molecular improvement of strawberries breeding.

  19. Production of transgenic pigs over-expressing the antiviral gene Mx1

    Directory of Open Access Journals (Sweden)

    Quanmei Yan

    2014-01-01

    Full Text Available The myxovirus resistance gene (Mx1 has a broad spectrum of antiviral activities. It is therefore an interesting candidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cell nuclear transfer (SCNT to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs express approximately 15–25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was also markedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs with influenza A virus and classical swine fever virus (CFSV. Indirect immunofluorescence assay (IFA revealed a profound decrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-fold reduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found that the Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These results demonstrate that the Mx1 transgene can protect against viral infection in cells of transgenic pigs and indicate that the Mx1 transgene can be harnessed to develop disease-resistant pigs.

  20. Improving xylitol production at elevated temperature with engineered Kluyveromyces marxianus through over-expressing transporters.

    Science.gov (United States)

    Zhang, Jia; Zhang, Biao; Wang, Dongmei; Gao, Xiaolian; Hong, Jiong

    2015-01-01

    Three transporter genes including Kluyveromyces marxianus aquaglyceroporin gene (KmFPS1), Candida intermedia glucose/xylose facilitator gene (CiGXF1) or glucose/xylose symporter gene (CiGXS1) were over-expressed in K. marxianus YZJ017 to improve xylitol production at elevated temperatures. The xylitol production of YZJ074 that harbored CiGXF1 was improved to 147.62g/L in Erlenmeyer flask at 42°C. In fermenter, 99.29 and 149.60g/L xylitol were produced from 99.55 and 151.91g/L xylose with productivity of 4.14 and 3.40g/L/h respectively at 42°C. Even at 45°C, YZJ074 could produce 101.30g/L xylitol from 101.41g/L xylose with productivity of 2.81g/L/h. Using fed-batch fermentation through repeatedly adding non-sterilized substrate directly, YZJ074 could produce 312.05g/L xylitol which is the highest yield reported to date. The engineered strains YZJ074 which can produce xylitol at elevated temperatures is an excellent foundation for xylitol bioconversion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Over expression of beta-1, 4-xylanase by auto-induction in E. coli

    International Nuclear Information System (INIS)

    Khan, M.I.K.; Sajjad, M.; Akhtar, W.

    2013-01-01

    Catalytic domain of β-1, 4-xylanase gene, (xynZ.CD) of Clostridium thermocellum was cloned in pET28a expression vector and over-expressed in Escherichia colt BL21 CodonPlus (RIL). The production of XynZ.CD in E. colt was optimized using different concentrations of lactose and induction of the enzyme at different stages of growth. The maximum growth of the cells and the enzyme activity were observed when the cells were induced with 10mM lactose after 8 hours of incubation. The enzyme was found to constitute >40% of the total cell proteins in the supernatant of the lysed cells transformed with recombinant pET28a/xynZ.CD. It was purified by heating the cell lysate at 65 degree C for 30 m followed by fractionation through FPLC. Molecular weight of XynZ.CD was found to be approximately 38,524 D by MALDI-TOF analysis. The enzyme variant was quite stable within broad pH range of 5.5 - 8.0 and it retained >85% of xylanase activity after 2 h incubation at 70 degre C. (author)

  2. Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

    Science.gov (United States)

    Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

    2018-06-07

    Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

  3. Enhanced water stress tolerance of transgenic maize plants over-expressing LEA Rab28 gene.

    Science.gov (United States)

    Amara, Imen; Capellades, Montserrat; Ludevid, M Dolors; Pagès, Montserrat; Goday, Adela

    2013-06-15

    Late Embryogenesis Abundant (LEA) proteins participate in plant stress responses and contribute to the acquisition of desiccation tolerance. In this report Rab28 LEA gene has been over-expressed in maize plants under a constitutive maize promoter. The expression of Rab28 transcripts led to the accumulation and stability of Rab28 protein in the transgenic plants. Native Rab28 protein is localized to nucleoli in wild type maize embryo cells; here we find by whole-mount immunocytochemistry that in root cells of Rab28 transgenic and wild-type plants the protein is also associated to nucleolar structures. Transgenic plants were tested for stress tolerance and resulted in sustained growth under polyethyleneglycol (PEG)-mediated dehydration compared to wild-type controls. Under osmotic stress transgenic seedlings showed increased leaf and root areas, higher relative water content (RWC), reduced chlorophyll loss and lower Malondialdehyde (MDA) production in relation to wild-type plants. Moreover, transgenic seeds exhibited higher germination rates than wild-type seeds under water deficit. Overall, our results highlight the presence of transgenic Rab28 protein in nucleolar structures and point to the potential of group 5 LEA Rab28 gene as candidate to enhance stress tolerance in maize plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. Over-expression of KdSOC1 gene affected plantlet morphogenesis in Kalanchoe daigremontiana.

    Science.gov (United States)

    Zhu, Chen; Wang, Li; Chen, Jinhua; Liu, Chenglan; Zeng, Huiming; Wang, Huafang

    2017-07-17

    Kalanchoe daigremontiana reproduces asexually by producing plantlets along the leaf margin. The aim of this study was to identify the function of the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 gene in Kalanchoe daigremontiana (KdSOC1) during plantlet morphogenesis. In this study, KdSOC1 gene expression was detected at stem cell niche during in vitro somatic embryogenesis and plantlet morphogenesis. Disrupting endogenous auxin transportation suppressed the KdSOC1 gene response. Knockdown of the KdSOC1 gene caused a defect in cotyledon formation during the early heart stage of somatic embryogenesis. Over-expression (OE) of the KdSOC1 gene resulted in asymmetric plantlet distribution, a reduced number of plantlets, thicker leaves, and thicker vascular fibers. Higher KdPIN1 gene expression and auxin content were found in OE plant compared to those of wild-type plant leaves, which indicated possible KdSOC1 gene role in affecting auxin distribution and accumulation. KdSOC1 gene OE in DR5-GUS Arabidopsis reporting lines resulted in an abnormal auxin response pattern during different stages of somatic embryogenesis. In summary, the KdSOC1 gene OE might alter auxin distribution and accumulation along leaf margin to initiate plantlet formation and distribution, which is crucial for plasticity during plantlet formation under various environmental conditions.

  5. Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells

    Science.gov (United States)

    Molenaar, Jan J.; Ebus, Marli E.; Geerts, Dirk; Koster, Jan; Lamers, Fieke; Valentijn, Linda J.; Westerhout, Ellen M.; Versteeg, Rogier; Caron, Huib N.

    2009-01-01

    Two genes have a synthetically lethal relationship when the silencing or inhibiting of 1 gene is only lethal in the context of a mutation or activation of the second gene. This situation offers an attractive therapeutic strategy, as inhibition of such a gene will only trigger cell death in tumor cells with an activated second oncogene but spare normal cells without activation of the second oncogene. Here we present evidence that CDK2 is synthetically lethal to neuroblastoma cells with MYCN amplification and over-expression. Neuroblastomas are childhood tumors with an often lethal outcome. Twenty percent of the tumors have MYCN amplification, and these tumors are ultimately refractory to any therapy. Targeted silencing of CDK2 by 3 RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells. Silencing of MYCN abrogated this apoptotic response in MYCN-amplified cells. Inversely, silencing of CDK2 in MYCN single copy cells did not trigger apoptosis, unless a MYCN transgene was activated. The MYCN induced apoptosis after CDK2 silencing was accompanied by nuclear stabilization of P53, and mRNA profiling showed up-regulation of P53 target genes. Silencing of P53 rescued the cells from MYCN-driven apoptosis. The synthetic lethality of CDK2 silencing in MYCN activated neuroblastoma cells can also be triggered by inhibition of CDK2 with a small molecule drug. Treatment of neuroblastoma cells with roscovitine, a CDK inhibitor, at clinically achievable concentrations induced MYCN-dependent apoptosis. The synthetically lethal relationship between CDK2 and MYCN indicates CDK2 inhibitors as potential MYCN-selective cancer therapeutics. PMID:19525400

  6. CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice.

    Directory of Open Access Journals (Sweden)

    Lixin Wang

    2011-02-01

    Full Text Available Corticotropin-releasing factor (CRF signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

  7. Analysis of membrane proteome and secretome in cells over-expressing ADAM17 using quantitative proteomics

    International Nuclear Information System (INIS)

    Kawahara, R.; Simabuco, F.M.; Yokoo, S.; Paes Leme, A.F.; Sherman, N.

    2012-01-01

    Full text: A disintegrin and metalloproteinase (ADAM) protease is involved in proteolytic ectodomain shedding of several membrane-associated proteins and modulation of key cell signaling pathways in the tumor microenvironment. In this study, we examined the effect of over-expressing the full length human ADAM17 in membrane and secreted proteins. To this end, we constructed a stable Flp-In T-RExHEK293 cells expressing ADAM17 by tetracycline induction. These cells were grown in Dulbeccos modified Eagles medium containing light lysine, arginine or heavy, L-Arg-13C615N4 and L-Lys -13C615N2 (SILAC: stable isotope labeling with amino acid in cell culture) media and they were treated with an ADAM17 activator, phorbolester (PMA). Controls such as Flp-In T-RExHEK293 cell without PMA treatment and without ADAM17 cloned were cultivated in light medium. The ADAM17 overexpression was induced with tetracycline 500 ng/ml for 24 hours. Cells in a heavy condition were treated with PMA 50 ng/ml for 1 hour and vehicle DMSO was used as control in a light cell condition. The extracellular media were collected, concentrated and used to evaluate the secretome and a cell surface biotinylation-based approach was used to capture cell surface-associated proteins. The biotinylated proteins were eluted with dithiothreitol, alkylated with iodoacetamide and then digested with trypsin. The resulting peptides were subjected to LC-MS/MS analysis on an ETD enabled Orbitrap Velos instrument. The results showed different proteins up or down regulated in membrane and secretome analysis which might represent potential molecules involved in signaling or ADAM17 regulation events. (author)

  8. Over-expression of 14-3-3zeta is an early event in oral cancer

    International Nuclear Information System (INIS)

    Matta, Ajay; Bahadur, Sudhir; Duggal, Ritu; Gupta, Siddhartha D; Ralhan, Ranju

    2007-01-01

    The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2. Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (p trend < 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells. Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer

  9. Design of a Flexible Hardware Interface for Multiple Remote Electronic practical Experiments of Virtual Laboratory

    Directory of Open Access Journals (Sweden)

    Farah Said

    2012-03-01

    Full Text Available The objective of this work is to present a new design of a Flexible Hardware Interface (FHI based on PID control techniques to use in a virtual laboratory. This flexible hardware interface allows the easy implementation of different and multiple remote electronic practical experiments for undergraduate engineering classes. This interface can be viewed as opened hardware architecture to easily develop simple or complex remote experiments in the electronic domain. The philosophy of the use of this interface can also be expanded to many other domains as optic experiments for instance. It is also demonstrated that software can be developed to enable remote measurements of electronic circuits or systems using only Web site Interface. Using standard browsers (such as Internet explorer, Firefox, Chrome or Safari, different students can have a remote access to different practical experiments at a time.

  10. Entrepreneurs Experience and Firm Innovativeness: Multiple Mediation of Attitudinal and Behavioral Competencies

    OpenAIRE

    Bernard Nassiuma; Jamin Masasabi; Denyse Snelder; Anne Nangulu

    2018-01-01

    This study was anchored on a postpositivism paradigm and the Theory of perceived attributes and individual innovativeness, regarding the multiple serial mediations of attitudinal and behavioral competencies in the relationship between the entrepreneurs’ experience and firm innovativeness. To test the hypothesized relationship a cross-sectional design and qualitative approach were employed. The study drew on a sample of 698 Micro and Small-scale entrepreneurs in Western Kenya. Questionnaires ...

  11. Multiple scattering and attenuation corrections in Deep Inelastic Neutron Scattering experiments

    International Nuclear Information System (INIS)

    Dawidowski, J; Blostein, J J; Granada, J R

    2006-01-01

    Multiple scattering and attenuation corrections in Deep Inelastic Neutron Scattering experiments are analyzed. The theoretical basis of the method is stated, and a Monte Carlo procedure to perform the calculation is presented. The results are compared with experimental data. The importance of the accuracy in the description of the experimental parameters is tested, and the implications of the present results on the data analysis procedures is examined

  12. The influence of multiple oppressions on women of color's experiences with insidious trauma.

    Science.gov (United States)

    Watson, Laurel B; DeBlaere, Cirleen; Langrehr, Kimberly J; Zelaya, David G; Flores, Mirella J

    2016-11-01

    In this study, we examined the relations between multiple forms of oppressive experiences (i.e., racism, sexism, and sexual objectification) and trauma symptoms among Women of Color (WOC). In addition, self-esteem was explored as a partial mediating variable in these links, and ethnic identity strength was proposed to buffer the negative relationship between multiple forms of oppression and self-esteem, and the positive relationship between oppressive experiences and trauma symptoms. Results suggested that self-esteem partially mediated the positive relationship between racist experiences and trauma symptoms, such that racism was related to lower self-esteem, which was then related to more trauma symptoms. Sexism and sexual objectification were directly linked with trauma symptoms. Moreover, average and high levels of ethnic identity strength buffered the positive link between racism and trauma symptoms. Consistent with an additive intersectionality framework, results demonstrate the importance of attending to multiple forms of oppression as they relate to trauma symptoms among WOC. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. MECHANISMS OF MRP OVER-EXPRESSION IN 4 HUMAN LUNG-CANCER CELL-LINES AND ANALYSIS OF THE MRP AMPLICON

    NARCIS (Netherlands)

    EIJDEMS, EWHM; DEHAAS, M; COCOMARTIN, JM; OTTENHEIM, CPE; ZAMAN, GJR; DAUWERSE, HG; BREUNING, MH; TWENTYMAN, PR; BORST, P; BAAS, F

    1995-01-01

    Some multidrug resistant cell lines over-express the gene encoding the multidrug-resistance-associated protein (MRP). In all cell lines reported thus far, over-expression is associated with gene amplification. We have studied the predominant mechanisms of MRP over-expression in 4 human lung-cancer

  14. Exploring Canadian Women's Multiple Abortion Experiences: Implications for Reducing Stigma and Improving Patient-Centered Care.

    Science.gov (United States)

    LaRoche, Kathryn J; Foster, Angel M

    2018-05-24

    Roughly one-third of all abortions in Canada are subsequent abortions. However, few published reports showcase women's voices or explore women's experiences on this topic. Our study aimed to understand better the ways that women who have had multiple abortions talk about and view those experiences. Between 2012 and 2016, we conducted in-depth interviews with 41 Canadian women who had a total of 87 abortions in the 5 years preceding the interviews. We audio-recorded and transcribed all English- and French-language interviews and analyzed our data for content and themes using a multiphased iterative approach and inductive and deductive techniques. Women described their abortion experiences as unique life events, even in cases when the overarching circumstances surrounding the pregnancies were similar. Participants recalled multiple factors that influenced their decisions to terminate, including their relationship status; level of support from family and friends; financial situation; health status; previous reproductive health, pregnancy, and abortion experiences; and desire to parent. In general, a previous abortion demystified the abortion process but did not play a significant role in decision making. Women described intensified feelings of shame and both internalized and externalized stigma surrounding their decision to have more than one abortion. However, the overwhelming majority were confident in their decisions. The often-used phase "repeat abortion" fails to capture women's experiences and the complex decision making surrounding each pregnancy. Efforts to reframe the narrative of multiple abortions, including among health care providers, could help reduce the amplified stigma associated with having more than one lifetime abortion. Copyright © 2018 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  15. Track reconstruction for the Mu3e experiment based on a novel Multiple Scattering fit

    Directory of Open Access Journals (Sweden)

    Kozlinskiy Alexandr

    2017-01-01

    Full Text Available The Mu3e experiment is designed to search for the lepton flavor violating decay μ+ → e+e+e−. The aim of the experiment is to reach a branching ratio sensitivity of 10−16. In a first phase the experiment will be performed at an existing beam line at the Paul-Scherrer Institute (Switzerland providing 108 muons per second, which will allow to reach a sensitivity of 2 · 10−15. The muons with a momentum of about 28 MeV/c are stopped and decay at rest on a target. The decay products (positrons and electrons with energies below 53MeV are measured by a tracking detector consisting of two double layers of 50 μm thin silicon pixel sensors. The high granularity of the pixel detector with a pixel size of 80 μm × 80 μm allows for a precise track reconstruction in the high multiplicity environment of the Mu3e experiment, reaching 100 tracks per reconstruction frame of 50 ns in the final phase of the experiment. To deal with such high rates and combinatorics, the Mu3e track reconstruction uses a novel fit algorithm that in the simplest case takes into account only the multiple scattering, which allows for a fast online tracking on a GPU based filter farm. An implementation of the 3-dimensional multiple scattering fit based on hit triplets is described. The extension of the fit that takes into account energy losses and pixel size is used for offline track reconstruction. The algorithm and performance of the offline track reconstruction based on a full Geant4 simulation of the Mu3e detector are presented.

  16. Maternity experiences of mothers with multiple disadvantages in England: A qualitative study.

    Science.gov (United States)

    McLeish, Jenny; Redshaw, Maggie

    2018-06-14

    Disadvantaged mothers and their babies are at increased risk of poor perinatal outcomes and have less positive experiences of maternity care. To explore the maternity care experiences of mothers with multiple disadvantages. A qualitative descriptive study based on semi-structured interviews with 40 mothers with multiple disadvantages, using thematic analysis. Four themes emerged: 'A confusing and frightening time', 'Longing to be respected as an individual', 'The importance of choice and control', and 'Needing trust to feel safe'. Mothers brought feelings of powerlessness and low self-esteem to their encounters with maternity professionals, which could be significantly worsened by disrespectful care. They needed support to navigate the complex maternity system. Positive experiences were much more likely where the mother had received continuity of care from a specialist midwife or small team. Mothers with multiple disadvantages value being treated as an individual, making informed choices, and feeling safe, but they may lack the confidence to ask questions or challenge disrespectful treatment. Training and supervision should enable maternity professionals to understand how confusing maternity care can be to very disadvantaged mothers. It should emphasise the need to provide accessible and empowering information and guidance to enable all mothers to make choices and understand the system. Leaders of maternity services need to do more to challenge negative staff attitudes and ensure that that all mothers are treated at all times with kindness, respect and dignity. Specialist midwives can deliver a high quality service to mothers experiencing multiple disadvantages. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. The effect of NMDA-NR2B receptor subunit over-expression on olfactory memory task performance in the mouse.

    Science.gov (United States)

    White, Theresa L; Youngentob, Steven L

    2004-09-17

    The N-methyl-D-aspartate (NMDA) receptor in the forebrain is thought to modulate some forms of memory formation, with the NR2B subunit being particularly relevant to this process. Relative to wild-type mice, transgenic animals in which the NR2B subunit was over-expressed demonstrate superior memory in a number of behavioral tasks, including object recognition [Nature 401 (1999) 63]. The purpose of the present study was to explore the generality of such phenomena, interpreted as the effect of increasing NR2B expression on the retention of other types of sensory-related information. To accomplish this, we focused our evaluation on the highly salient sensory modality of olfaction. In the first experiment, mice performed both a novel-object-recognition task identical to that performed by Tang et al. [Nature 401 (1999) 63] and a novel-odor-recognition task analogously constructed. Although the results of the object recognition task were consistent with the previous literature, there was no evidence of an effect of NR2B over-expression on the retention of odor recognition memory in the specific task performed. As it was possible that, unlike object recognition memory, novel odor recognition is not NMDA-receptor-dependent, a second task was designed using the social transmission of food preference paradigm. In contrast to the foregoing olfactory task, there is evidence that the latter procedure is, indeed, NMDA-dependent. The results of the second study demonstrated that transgenic mice with NR2B over-expression had a clear memory advantage in this alternative odor memory paradigm. Taken together, these results suggest the NR2B subunit is an important component in some but not all forms of olfactory memory organization. Moreover, for those functions that are NMDA-receptor-dependent, these data support the growing literature demonstrating the importance of the NR2B subunit.

  18. LncRNA CCAT2 promotes tumorigenesis by over-expressed Pokemon in non-small cell lung cancer.

    Science.gov (United States)

    Zhao, Zhihong; Wang, Ju; Wang, Shengfa; Chang, Hao; Zhang, Tiewa; Qu, Junfeng

    2017-03-01

    Non-small cell lung cancer (NSCLC) remains one of the most important death-related diseases, with poor effective diagnosis and less therapeutic biomarkers. LncRNA colon cancer-associated transcript 2 (CCAT2) was identified as an oncogenic lncRNA and over-expressed in many tumor cells. The aims of this study were to detect the correlation between CCAT2 and its regulatory genes and then explore the potential mechanism between them in NSCLC. In this study, qRT-PCR was used to detect CCAT2, Pokemon and p21 expression. Western-blot was used to detect protein levels of Pokemon and p21. CCK-8 assay and Transwell chambers were used to assess cell viability and invasion. CCAT2 and Pokemon were over-expressed in NSCLC tissue and cells. In NSCLC cells, CCAT2 knockdown significantly decreased cell viability and invasion as well as Pokemon expression, but increased the expression of p21; then CCAT2 overexpression revealed an opposite result. In addition, over-expressed Pokemon reversed the results that induced by si-CCAT2, while down-regulation of Pokemon significantly reversed the results that induced by CCAT2 overexpression. The results indicated that CCAT2 promotes tumorigenesis by over-expression of Pokemon, and the potential mechanism might relate to the Pokemon related gene p21. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

    Science.gov (United States)

    Zhang, Hui; Ma, Li; Yin, Yan-Ling; Dong, Lian-Qiang; Cheng, Gang-Ge; Ma, Ya-Qun; Li, Yun-Feng; Xu, Bai-Nan

    2016-09-01

    The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo.

    Science.gov (United States)

    Son, Marjatta; Fu, Qiao; Puttaparthi, Krishna; Matthews, Christina M; Elliott, Jeffrey L

    2009-04-01

    Over-expression of CCS in G93A SOD1 mice accelerates neurological disease and enhances mitochondrial pathology. We studied the effect of CCS over-expression in transgenic mice expressing G37R, G86R or L126Z SOD1 mutations in order to understand factors which influence mitochondrial dysfunction. Over-expression of CCS markedly decreased survival and produced mitochondrial vacuolation in G37R SOD1 mice but not in G86R or L126Z SOD1 mice. Moreover, CCS/G37R SOD1 spinal cord showed specific reductions in mitochondrial complex IV subunits consistent with an isolated COX deficiency, while no such reductions were detected in CCS/G86R or CCS/L126Z SOD1 mice. CCS over-expression increased the ratio of reduced to oxidized SOD1 monomers in the spinal cords of G37R SOD1 as well as G93A SOD1 mice, but did not influence the redox state of G86R or L126Z SOD1 monomers. The effects of CCS on disease are SOD1 mutation dependent and correlate with SOD1 redox susceptibility.

  1. Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

    Science.gov (United States)

    Mansour, J K; Beaudry, J L; Lindsay, R C L

    2017-12-01

    Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

  2. NOTES performed using multiple ports of entry: Current experience and potential implications for urologic applications.

    Science.gov (United States)

    Lima, Estevao; Rolanda, Carla; Correia-Pinto, Jorge

    2009-05-01

    An isolated transgastric port raises serious limitations in performing natural orifice translumenal endoscopic surgery (NOTES) complex procedures in the urology field. In an attempt to overcome these limitations, several solutions has been advanced, such as the hybrid approach (adding a single abdominal port access) or the pure NOTES combined approach (joining multiple natural orifice ports). To review the current state of experimental and clinical results of multiple ports in NOTES, a literature search of PubMed was performed, seeking publications from January 2002 to 2008 on NOTES. In addition, we looked at pertinent abstracts of annual meetings of the American Urological Association, the European Association of Urology, and the World Congress of Endourology from 2007. Multiple ports of entry seem to be necessary, mainly for moderately complex procedures. Thus, we could find studies using the hybrid approach (combination of transgastric or transvaginal access with a single transabdominal port), or using the pure NOTES combined approach (transgastric and transvesical, transvaginal and transcolonic, or transgastric and transvaginal). There is still limited experience in humans using these approaches, and no comparative studies exist to date. It is predictable that for moderately complex procedures, we will need multiple ports, so the transvaginal-transabdominal (hybrid) approach is the most appealing, whereas in a pure NOTES perspective, the transgastric-transvesical approach seems to be the preferred approach. We are waiting for new equipment and instruments that are more appropriate for these novel techniques.

  3. Charged particle multiplicity distributions in Au-Au collisions at RHIC-BNL energies (BRAHMS Experiment)

    International Nuclear Information System (INIS)

    Argintaru, D.; Bearden, I.G.; Beavis, D.

    2002-01-01

    The BRAHMS Experiment (Broad RAnge Hadronic Magnetic Spectrometers) takes place at the Relativistic Heavy Ion Collider (RHIC) from Brookhaven National Laboratory and searches for a transition of matter into a new phase called quark-gluon plasma (QGP), a phase transition that appears in extreme conditions of nuclear matter densities and temperatures. Important signals for this transition are related to dependencies of the charged particle multiplicity distributions on the pseudorapidity range. The charged particle multiplicity distributions in Au-Au collisions at RHIC energies are obtained from the global detector measurements. These detectors are: - An array of Si strip detectors and scintillation tiles placed around the interaction region; they cover the range η < 2 in pseudorapidity, measuring the majority of charged particles; - Two systems of Cerenkov detectors (Beam-Beam Counters) placed both sides of the nominal interaction point at 220 cm and cover the range 3 < η < 4.3 in pseudorapidity. These detectors are used for vertex determination and supply a level zero trigger for the entire experiment; - Zero Degree Calorimeters placed at zero degree with respect to the beam axis, both sides of the vertex, measuring the spectator neutrons from the nuclear reactions. These detectors supplies information about the reaction centrality and could estimate the interaction vertex. The paper presents some results on charged particle multiplicities in different pseudorapidity ranges at different impact parameters. Interesting dependencies of the average charged particle multiplicities on the pseudorapidity range, impact parameters and total available energy in the centre of mass system. Some comparisons with the simulation codes predictions and theoretical model estimations are included, too. (authors)

  4. Error analysis of dimensionless scaling experiments with multiple points using linear regression

    International Nuclear Information System (INIS)

    Guercan, Oe.D.; Vermare, L.; Hennequin, P.; Bourdelle, C.

    2010-01-01

    A general method of error estimation in the case of multiple point dimensionless scaling experiments, using linear regression and standard error propagation, is proposed. The method reduces to the previous result of Cordey (2009 Nucl. Fusion 49 052001) in the case of a two-point scan. On the other hand, if the points follow a linear trend, it explains how the estimated error decreases as more points are added to the scan. Based on the analytical expression that is derived, it is argued that for a low number of points, adding points to the ends of the scanned range, rather than the middle, results in a smaller error estimate. (letter)

  5. Sintering equation: determination of its coefficients by experiments - using multiple regression

    International Nuclear Information System (INIS)

    Windelberg, D.

    1999-01-01

    Sintering is a method for volume-compression (or volume-contraction) of powdered or grained material applying high temperature (less than the melting point of the material). Maekipirtti tried to find an equation which describes the process of sintering by its main parameters sintering time, sintering temperature and volume contracting. Such equation is called a sintering equation. It also contains some coefficients which characterise the behaviour of the material during the process of sintering. These coefficients have to be determined by experiments. Here we show that some linear regressions will produce wrong coefficients, but multiple regression results in an useful sintering equation. (orig.)

  6. Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders

    DEFF Research Database (Denmark)

    Büssing, Arndt; Wirth, Anne Gritli; Reiser, Franz

    2014-01-01

    Background: Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty...... spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 +/- 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Results: Among...... participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F = 9...

  7. Neophyte experiences of football (soccer) match analysis: a multiple case study approach.

    Science.gov (United States)

    McKenna, Mark; Cowan, Daryl Thomas; Stevenson, David; Baker, Julien Steven

    2018-03-05

    Performance analysis is extensively used in sport, but its pedagogical application is little understood. Given its expanding role across football, this study explored the experiences of neophyte performance analysts. Experiences of six analysis interns, across three professional football clubs, were investigated as multiple cases of new match analysis. Each intern was interviewed after their first season, with archival data providing background information. Four themes emerged from qualitative analysis: (1) "building of relationships" was important, along with trust and role clarity; (2) "establishing an analysis system" was difficult due to tacit coach knowledge, but analysis was established; (3) the quality of the "feedback process" hinged on coaching styles, with balance of feedback and athlete engagement considered essential; (4) "establishing effect" was complex with no statistical effects reported; yet enhanced relationships, role clarity, and improved performances were reported. Other emic accounts are required to further understand occupational culture within performance analysis.

  8. Over-expression of Trxo1 increases the viability of tobacco BY-2 cells under H2O2 treatment.

    Science.gov (United States)

    Ortiz-Espín, Ana; Locato, Vittoria; Camejo, Daymi; Schiermeyer, Andreas; De Gara, Laura; Sevilla, Francisca; Jiménez, Ana

    2015-09-01

    Reactive oxygen species (ROS), especially hydrogen peroxide, play a critical role in the regulation of plant development and in the induction of plant defence responses during stress adaptation, as well as in plant cell death. The antioxidant system is responsible for controlling ROS levels in these processes but redox homeostasis is also a key factor in plant cell metabolism under normal and stress situations. Thioredoxins (Trxs) are ubiquitous small proteins found in different cell compartments, including mitochondria and nuclei (Trxo1), and are involved in the regulation of target proteins through reduction of disulphide bonds, although their role under oxidative stress has been less well studied. This study describes over-expression of a Trxo1 for the first time, using a cell-culture model subjected to an oxidative treatment provoked by H2O2. Control and over-expressing PsTrxo1 tobacco (Nicotiana tabacum) BY-2 cells were treated with 35 mm H2O2 and the effects were analysed by studying the growth dynamics of the cultures together with oxidative stress parameters, as well as several components of the antioxidant systems involved in the metabolism of H2O2. Analysis of different hallmarks of programmed cell death was also carried out. Over-expression of PsTrxo1 caused significant differences in the response of TBY-2 cells to high concentrations of H2O2, namely higher and maintained viability in over-expressing cells, whilst the control line presented a severe decrease in viability and marked indications of oxidative stress, with generalized cell death after 3 d of treatment. In over-expressing cells, an increase in catalase activity, decreases in H2O2 and nitric oxide contents and maintenance of the glutathione redox state were observed. A decreased content of endogenous H2O2 may be responsible in part for the delayed cell death found in over-expressing cells, in which changes in oxidative parameters and antioxidants were less extended after the oxidative

  9. Damping-tunable energy-harvesting vehicle damper with multiple controlled generators: Design, modeling and experiments

    Science.gov (United States)

    Xie, Longhan; Li, Jiehong; Li, Xiaodong; Huang, Ledeng; Cai, Siqi

    2018-01-01

    Hydraulic dampers are used to decrease the vibration of a vehicle, where vibration energy is dissipated as heat. In addition to resulting in energy waste, the damping coefficient in hydraulic dampers cannot be changed during operation. In this paper, an energy-harvesting vehicle damper was proposed to replace traditional hydraulic dampers. The goal is not only to recover kinetic energy from suspension vibration but also to change the damping coefficient during operation according to road conditions. The energy-harvesting damper consists of multiple generators that are independently controlled by switches. One of these generators connects to a tunable resistor for fine tuning the damping coefficient, while the other generators are connected to a control and rectifying circuit, each of which both regenerates electricity and provides a constant damping coefficient. A mathematical model was built to investigate the performance of the energy-harvesting damper. By controlling the number of switched-on generators and adjusting the value of the external tunable resistor, the damping can be fine tuned according to the requirement. In addition to the capability of damping tuning, the multiple controlled generators can output a significant amount of electricity. A prototype was built to test the energy-harvesting damper design. Experiments on an MTS testing system were conducted, with results that validated the theoretical analysis. Experiments show that changing the number of switched-on generators can obviously tune the damping coefficient of the damper and simultaneously produce considerable electricity.

  10. Impulsive response of an automatic transmission system with multiple clearances: Formulation, simulation and experiment

    Science.gov (United States)

    Crowther, Ashley R.; Singh, Rajendra; Zhang, Nong; Chapman, Chris

    2007-10-01

    Impulsive responses in geared systems with multiple clearances are studied when the mean torque excitation and system load change abruptly, with application to a vehicle driveline with an automatic transmission. First, torsional lumped-mass models of the planetary and differential gear sets are formulated using matrix elements. The model is then reduced to address tractable nonlinear problems while successfully retaining the main modes of interest. Second, numerical simulations for the nonlinear model are performed for transient conditions and a typical driving situation that induces an impulsive behaviour simulated. However, initial conditions and excitation and load profiles have to be carefully defined before the model can be numerically solved. It is shown that the impacts within the planetary or differential gears may occur under combinations of engine, braking and vehicle load transients. Our analysis shows that the shaping of the engine transient by the torque converter before reaching the clearance locations is more critical. Third, a free vibration experiment is developed for an analogous driveline with multiple clearances and three experiments that excite different response regimes have been carried out. Good correlations validate the proposed methodology.

  11. Robust design method and thermostatic experiment for multiple piezoelectric vibration absorber system

    International Nuclear Information System (INIS)

    Nambu, Yohsuke; Takashima, Toshihide; Inagaki, Akiya

    2015-01-01

    This paper examines the effects of connecting multiplexing shunt circuits composed of inductors and resistors to piezoelectric transducers so as to improve the robustness of a piezoelectric vibration absorber (PVA). PVAs are well known to be effective at suppressing the vibration of an adaptive structure; their weakness is low robustness to changes in the dynamic parameters of the system, including the main structure and the absorber. In the application to space structures, the temperature-dependency of capacitance of piezoelectric ceramics is the factor that causes performance reduction. To improve robustness to the temperature-dependency of the capacitance, this paper proposes a multiple-PVA system that is composed of distributed piezoelectric transducers and several shunt circuits. The optimization problems that determine both the frequencies and the damping ratios of the PVAs are multi-objective problems, which are solved using a real-coded genetic algorithm in this paper. A clamped aluminum beam with four groups of piezoelectric ceramics attached was considered in simulations and experiments. Numerical simulations revealed that the PVA systems designed using the proposed method had tolerance to changes in the capacitances. Furthermore, experiments using a thermostatic bath were conducted to reveal the effectiveness and robustness of the PVA systems. The maximum peaks of the transfer functions of the beam with the open circuit, the single-PVA system, the double-PVA system, and the quadruple-PVA system at 20 °C were 14.3 dB, −6.91 dB, −7.47 dB, and −8.51 dB, respectively. The experimental results also showed that the multiple-PVA system is more robust than a single PVA in a variable temperature environment from −10 °C to 50 °C. In conclusion, the use of multiple PVAs results in an effective, robust vibration control method for adaptive structures. (paper)

  12. A permutation-based multiple testing method for time-course microarray experiments

    Directory of Open Access Journals (Sweden)

    George Stephen L

    2009-10-01

    Full Text Available Abstract Background Time-course microarray experiments are widely used to study the temporal profiles of gene expression. Storey et al. (2005 developed a method for analyzing time-course microarray studies that can be applied to discovering genes whose expression trajectories change over time within a single biological group, or those that follow different time trajectories among multiple groups. They estimated the expression trajectories of each gene using natural cubic splines under the null (no time-course and alternative (time-course hypotheses, and used a goodness of fit test statistic to quantify the discrepancy. The null distribution of the statistic was approximated through a bootstrap method. Gene expression levels in microarray data are often complicatedly correlated. An accurate type I error control adjusting for multiple testing requires the joint null distribution of test statistics for a large number of genes. For this purpose, permutation methods have been widely used because of computational ease and their intuitive interpretation. Results In this paper, we propose a permutation-based multiple testing procedure based on the test statistic used by Storey et al. (2005. We also propose an efficient computation algorithm. Extensive simulations are conducted to investigate the performance of the permutation-based multiple testing procedure. The application of the proposed method is illustrated using the Caenorhabditis elegans dauer developmental data. Conclusion Our method is computationally efficient and applicable for identifying genes whose expression levels are time-dependent in a single biological group and for identifying the genes for which the time-profile depends on the group in a multi-group setting.

  13. Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

    Science.gov (United States)

    Xu, Jian-zhong; Zhang, Wei-guo

    2016-01-01

    With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

  14. Over-expression of SlJA2 decreased heat tolerance of transgenic tobacco plants via salicylic acid pathway.

    Science.gov (United States)

    Liu, Zhong-Ming; Yue, Meng-Meng; Yang, Dong-Yue; Zhu, Shao-Bo; Ma, Na-Na; Meng, Qing-Wei

    2017-04-01

    Over-expression of SlJA2 decreased the accumulation of SA, which resulted in significant physiological and gene expression changes in transgenic tobacco plants, leading to the decreased heat tolerance of transgenic tobacco. NAC family, the largest transcription factors in plants, responses to different environmental stimuli. Here, we isolated a typical NAC transcription factor (SlJA2) from tomato and got transgenic tobacco with SlJA2 over-expression. Expression of SlJA2 was induced by heat stress (42 °C), chilling stress (4 °C), drought stress, osmotic stress, abscisic acid, and salicylic acid. Over-expression of SlJA2 decreased the accumulation of salicylic acid by regulating expression of salicylic acid degradation gene under heat stress. Compared to WT plants, stomatal apertures and water loss increased in transgenic plants, and the damage of photosynthetic apparatus and chlorophyll breakdown were more serious in transgenic plants under heat stress. Meanwhile, more H 2 O 2 and O 2 ·- were accumulated transgenic plants and proline synthesis was restricted, which resulted in more serious oxidative damage compared to WT. qRT-PCR analysis showed that over-expression of SlJA2 could down-regulate genes involved in reactive oxygen species scavenging, proline biosynthesis, and response to heat stress. All the above results indicated that SlJA2 may be a negative regulator responded to plant's heat tolerance. Thus, this study provides new insight into roles of NAC family member in plant response to abiotic stress.

  15. Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

    NARCIS (Netherlands)

    Visser, Leo H.; Heerings, Marco A.; Jongen, Peter J.; van der Hiele, Karin

    2016-01-01

    Background: The adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study

  16. Capturing the experiences of patients across multiple complex interventions: a meta-qualitative approach.

    Science.gov (United States)

    Webster, Fiona; Christian, Jennifer; Mansfield, Elizabeth; Bhattacharyya, Onil; Hawker, Gillian; Levinson, Wendy; Naglie, Gary; Pham, Thuy-Nga; Rose, Louise; Schull, Michael; Sinha, Samir; Stergiopoulos, Vicky; Upshur, Ross; Wilson, Lynn

    2015-09-08

    The perspectives, needs and preferences of individuals with complex health and social needs can be overlooked in the design of healthcare interventions. This study was designed to provide new insights on patient perspectives drawing from the qualitative evaluation of 5 complex healthcare interventions. Patients and their caregivers were recruited from 5 interventions based in primary, hospital and community care in Ontario, Canada. We included 62 interviews from 44 patients and 18 non-clinical caregivers. Our team analysed the transcripts from 5 distinct projects. This approach to qualitative meta-evaluation identifies common issues described by a diverse group of patients, therefore providing potential insights into systems issues. This study is a secondary analysis of qualitative data; therefore, no outcome measures were identified. We identified 5 broad themes that capture the patients' experience and highlight issues that might not be adequately addressed in complex interventions. In our study, we found that: (1) the emergency department is the unavoidable point of care; (2) patients and caregivers are part of complex and variable family systems; (3) non-medical issues mediate patients' experiences of health and healthcare delivery; (4) the unanticipated consequences of complex healthcare interventions are often the most valuable; and (5) patient experiences are shaped by the healthcare discourses on medically complex patients. Our findings suggest that key assumptions about patients that inform intervention design need to be made explicit in order to build capacity to better understand and support patients with multiple chronic diseases. Across many health systems internationally, multiple models are being implemented simultaneously that may have shared features and target similar patients, and a qualitative meta-evaluation approach, thus offers an opportunity for cumulative learning at a system level in addition to informing intervention design and

  17. Characterization of a human cell line stably over-expressing the candidate oncogene, dual specificity phosphatase 12.

    Directory of Open Access Journals (Sweden)

    Erica L Cain

    2011-04-01

    Full Text Available Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6 and the dual specificity phosphatase 12 (dusp12. While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1 which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted.

  18. Over-expression of a cytochrome P450 is associated with resistance to pyriproxyfen in the greenhouse whitefly Trialeurodes vaporariorum.

    Directory of Open Access Journals (Sweden)

    Nikos Karatolos

    Full Text Available The juvenile hormone mimic, pyriproxyfen is a suppressor of insect embryogenesis and development, and is effective at controlling pests such as the greenhouse whitefly Trialeurodes vaporariorum (Westwood which are resistant to other chemical classes of insecticides. Although there are reports of insects evolving resistance to pyriproxyfen, the underlying resistance mechanism(s are poorly understood.Bioassays against eggs of a German (TV8 population of T. vaporariorum revealed a moderate level (21-fold of resistance to pyriproxyfen. This is the first time that pyriproxyfen resistance has been confirmed in this species. Sequential selection of TV8 rapidly generated a strain (TV8pyrsel displaying a much higher resistance ratio (>4000-fold. The enzyme inhibitor piperonyl butoxide (PBO suppressed this increased resistance, indicating that it was primarily mediated via metabolic detoxification. Microarray analysis identified a number of significantly over-expressed genes in TV8pyrsel as candidates for a role in resistance including cytochrome-P450 dependent monooxygenases (P450s. Quantitative PCR highlighted a single P450 gene (CYP4G61 that was highly over-expressed (81.7-fold in TV8pyrsel.Over-expression of a single cytochrome P450 gene (CYP4G61 has emerged as a strong candidate for causing the enhanced resistance phenotype. Further work is needed to confirm the role of the encoded P450 enzyme CYP4G61 in detoxifying pyriproxyfen.

  19. Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice.

    Science.gov (United States)

    Wang, Jian; Menchenton, Trevor; Yin, Shankai; Yu, Zhiping; Bance, Manohar; Morris, David P; Moore, Craig S; Korneluk, Robert G; Robertson, George S

    2010-07-01

    Apoptosis of cochlear cells plays a significant role in age-related hearing loss or presbycusis. In this study, we evaluated whether over-expression of the anti-apoptotic protein known as X-linked Inhibitor of Apoptosis Protein (XIAP) slows the development of presbycusis. We compared the age-related hearing loss between transgenic (TG) mice that over-express human XIAP tagged with 6-Myc (Myc-XIAP) on a pure C57BL/6J genetic background with wild-type (WT) littermates by measuring auditory brainstem responses. The result showed that TG mice developed hearing loss considerably more slowly than WT littermates, primarily within the high-frequency range. The average total hair cell loss was significantly less in TG mice than WT littermates. Although levels of Myc-XIAP in the ear remained constant at 2 and 14 months, there was a marked increase in the amount of endogenous XIAP from 2 to 14 months in the cochlea, but not in the brain, in both genotypes. These results suggest that XIAP over-expression reduces age-related hearing loss and hair cell death in the cochlea. Copyright 2008 Elsevier Inc. All rights reserved.

  20. Enhancing cytochrome P450-mediated conversions in P. pastoris through RAD52 over-expression and optimizing the cultivation conditions.

    Science.gov (United States)

    Wriessnegger, Tamara; Moser, Sandra; Emmerstorfer-Augustin, Anita; Leitner, Erich; Müller, Monika; Kaluzna, Iwona; Schürmann, Martin; Mink, Daniel; Pichler, Harald

    2016-04-01

    Cytochrome P450 enzymes (CYPs) play an essential role in the biosynthesis of various natural compounds by catalyzing regio- and stereospecific hydroxylation reactions. Thus, CYP activities are of great interest in the production of fine chemicals, pharmaceutical compounds or flavors and fragrances. Industrial applicability of CYPs has driven extensive research efforts aimed at improving the performance of these enzymes to generate robust biocatalysts. Recently, our group has identified CYP-mediated hydroxylation of (+)-valencene as a major bottleneck in the biosynthesis of trans-nootkatol and (+)-nootkatone in Pichia pastoris. In the current study, we aimed at enhancing CYP-mediated (+)-valencene hydroxylation by over-expressing target genes identified through transcriptome analysis in P. pastoris. Strikingly, over-expression of the DNA repair and recombination gene RAD52 had a distinctly positive effect on trans-nootkatol formation. Combining RAD52 over-expression with optimization of whole-cell biotransformation conditions, i.e. optimized media composition and cultivation at higher pH value, enhanced trans-nootkatol production 5-fold compared to the initial strain and condition. These engineering approaches appear to be generally applicable for enhanced hydroxylation of hydrophobic compounds in P. pastoris as confirmed here for two additional membrane-attached CYPs, namely the limonene-3-hydroxylase from Mentha piperita and the human CYP2D6. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival

    Directory of Open Access Journals (Sweden)

    Lincoln Douglas

    2006-06-01

    Full Text Available Abstract Background Increased expression of Eph receptor tyrosine kinases and their ephrin ligands has been implicated in tumor progression in a number of malignancies. This report describes aberrant expression of these genes in ovarian cancer, the commonest cause of death amongst gynaecological malignancies. Methods Eph and ephrin expression was determined using quantitative real time RT-PCR. Correlation of gene expression was measured using Spearman's rho statistic. Survival was analysed using log-rank analysis and (was visualised by Kaplan-Meier survival curves. Results Greater than 10 fold over-expression of EphA1 and a more modest over-expression of EphA2 were observed in partially overlapping subsets of tumors. Over-expression of EphA1 strongly correlated (r = 0.801; p Conclusion These data imply that increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive tumor phenotype. The known functions of Eph/ephrin signalling in cell de-adhesion and movement may explain the observed correlation of ephrin expression with poor prognosis.

  2. A silicon multiplicity detector system for an experiment on the interaction of antiprotons with nuclei at BNL

    International Nuclear Information System (INIS)

    Ahmad, S.; Bonner, B.E.; Buchanan, J.A.; Clement, J.M.; Empl, A.; Mutchler, G.S.; Toshkov, S.; Chan, C.S.; Kramer, M.A.; Lindenbaum, S.J.; Hallman, T.J.; Madansky, L.; Peaslee, D.C.

    1991-01-01

    A Large Angle Multiplicity Detector (LAMD) system has been developed and used at the BNL experiment E854: Antiproton Nucleus Interactions. This system performed well with an energetic antiproton beam. Charged particle multiplicity distributions from pbar annihilations were measured. We discuss the design and performance of the LAMD system in this paper. 6 refs., 10 figs

  3. Identification of potential biomarkers from microarray experiments using multiple criteria optimization

    International Nuclear Information System (INIS)

    Sánchez-Peña, Matilde L; Isaza, Clara E; Pérez-Morales, Jaileene; Rodríguez-Padilla, Cristina; Castro, José M; Cabrera-Ríos, Mauricio

    2013-01-01

    Microarray experiments are capable of determining the relative expression of tens of thousands of genes simultaneously, thus resulting in very large databases. The analysis of these databases and the extraction of biologically relevant knowledge from them are challenging tasks. The identification of potential cancer biomarker genes is one of the most important aims for microarray analysis and, as such, has been widely targeted in the literature. However, identifying a set of these genes consistently across different experiments, researches, microarray platforms, or cancer types is still an elusive endeavor. Besides the inherent difficulty of the large and nonconstant variability in these experiments and the incommensurability between different microarray technologies, there is the issue of the users having to adjust a series of parameters that significantly affect the outcome of the analyses and that do not have a biological or medical meaning. In this study, the identification of potential cancer biomarkers from microarray data is casted as a multiple criteria optimization (MCO) problem. The efficient solutions to this problem, found here through data envelopment analysis (DEA), are associated to genes that are proposed as potential cancer biomarkers. The method does not require any parameter adjustment by the user, and thus fosters repeatability. The approach also allows the analysis of different microarray experiments, microarray platforms, and cancer types simultaneously. The results include the analysis of three publicly available microarray databases related to cervix cancer. This study points to the feasibility of modeling the selection of potential cancer biomarkers from microarray data as an MCO problem and solve it using DEA. Using MCO entails a new optic to the identification of potential cancer biomarkers as it does not require the definition of a threshold value to establish significance for a particular gene and the selection of a normalization

  4. Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

    Science.gov (United States)

    Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

    2009-01-01

    Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

  5. Benchmarking in a differentially heated rotating annulus experiment: Multiple equilibria in the light of laboratory experiments and simulations

    Science.gov (United States)

    Vincze, Miklos; Harlander, Uwe; Borchert, Sebastian; Achatz, Ulrich; Baumann, Martin; Egbers, Christoph; Fröhlich, Jochen; Hertel, Claudia; Heuveline, Vincent; Hickel, Stefan; von Larcher, Thomas; Remmler, Sebastian

    2014-05-01

    modes. Thus certain "benchmarks" have been created that can later be used as test cases for atmospheric numerical model validation. Both in the experiments and in the numerics multiple equilibrium states have been observed in the form of hysteretic behavior depending on the initial conditions. The precise quantification of these state and wave mode transitions may shed light to some aspects of the basic underlying dynamics of the baroclinic annulus configuration, still to be understood.

  6. Computer experiments of the time-sequence of individual steps in multiple Coulomb-excitation

    International Nuclear Information System (INIS)

    Boer, J. de; Dannhaueser, G.

    1982-01-01

    The way in which the multiple E2 steps in the Coulomb-excitation of a rotational band of a nucleus follow one another is elucidated for selected examples using semiclassical computer experiments. The role a given transition plays for the excitation of a given final state is measured by a quantity named ''importance function''. It is found that these functions, calculated for the highest rotational state, peak at times forming a sequence for the successive E2 transitions starting from the ground state. This sequential behaviour is used to approximately account for the effects on the projectile orbit of the sequential transfer of excitation energy and angular momentum from projectile to target. These orbits lead to similar deflection functions and cross sections as those obtained from a symmetrization procedure approximately accounting for the transfer of angular momentum and energy. (Auth.)

  7. A Bayesian decision procedure for testing multiple hypotheses in DNA microarray experiments.

    Science.gov (United States)

    Gómez-Villegas, Miguel A; Salazar, Isabel; Sanz, Luis

    2014-02-01

    DNA microarray experiments require the use of multiple hypothesis testing procedures because thousands of hypotheses are simultaneously tested. We deal with this problem from a Bayesian decision theory perspective. We propose a decision criterion based on an estimation of the number of false null hypotheses (FNH), taking as an error measure the proportion of the posterior expected number of false positives with respect to the estimated number of true null hypotheses. The methodology is applied to a Gaussian model when testing bilateral hypotheses. The procedure is illustrated with both simulated and real data examples and the results are compared to those obtained by the Bayes rule when an additive loss function is considered for each joint action and the generalized loss 0-1 function for each individual action. Our procedure significantly reduced the percentage of false negatives whereas the percentage of false positives remains at an acceptable level.

  8. Probing nuclear shell structure beyond the N=40 subshell using multiple Coulomb excitation and transfer experiments

    Energy Technology Data Exchange (ETDEWEB)

    Hellgartner, Stefanie Christine

    2015-11-13

    In this work, the N=40 subshell closure is investigated with two complementary methods using a radioactive {sup 72}Zn ISOLDE beam: One- and two-neutron transfer reactions and multiple Coulomb excitation. In the one-neutron transfer reaction, two new levels of {sup 73}Zn were discovered. The two-neutron transfer channel allowed to study the differential cross section of the ground state and the 2{sup +}{sub 1} state of {sup 74}Zn. In the Coulomb excitation experiment, the measured B(E2) values and quadrupole moments of {sup 72}Zn showed that the yrast states 0{sup +}{sub 1}, 2{sup +}{sub 1} and 4{sup +}{sub 1} are moderately collective. Contrary, the 0{sup +}{sub 2} state has a different structure, since it features a stronger closed N=40 configuration compared to the ground state.

  9. A qualitative study of cognitive behavioural therapy in multiple sclerosis: experiences of psychotherapists.

    Science.gov (United States)

    Ytterberg, Charlotte; Chruzander, Charlotte; Backenroth, Gunnel; Kierkegaard, Marie; Ahlström, Gerd; Gottberg, Kristina

    2017-12-01

    To investigate how psychotherapists experience using individual, face-to-face cognitive behavioural therapy (CBT) aimed at alleviating depressive symptoms in persons with multiple sclerosis (MS). Semi-structured interviews with three psychotherapists were conducted after CBT with 12 participants with MS, and analysed using qualitative content analysis. Two main themes emerged: Trusting their expertise as psychotherapists whilst lacking MS-specific knowledge, and The process of exploring the participants' readiness for CBT with modifications of content and delivery. The psychotherapists perceived it difficult to know whether a symptom was attributable to depression or to MS, and for some participants the CBT needed to be adapted to a more concrete content. Psychotherapists may need more MS-specific knowledge and an insight into the individual's functioning. The content of CBT in terms of concrete home assignments and behavioural activation needs to be individualised.

  10. Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples.

    Science.gov (United States)

    Vaarala, M H; Porvari, K S; Kyllönen, A P; Mustonen, M V; Lukkarinen, O; Vihko, P T

    1998-09-25

    A cDNA library specific for mRNA over-expressed in prostate cancer was generated by subtractive hybridization of transcripts originating from prostatic hyperplasia and cancer tissues. cDNA encoding ribosomal proteins L4, L5, L7a, L23a, L30, L37, S14 and S18 was found to be present among 100 analyzed clones. Levels of ribosomal mRNA were significantly higher at least in one of the prostate-cancer cell lines, LNCaP, DU-145 and PC-3, than in hyperplastic tissue, as determined by slot-blot hybridization. Furthermore, L23a- and S14-transcript levels were significantly elevated in PC-3 cells as compared with those in the normal prostate epithelial cell line PrEC. Generally, dramatic changes in the mRNA content of the ribosomal proteins were not detected, the most evident over-expression being that of L37 mRNA, which was 3.4 times more abundant in LNCaP cells than in hyperplastic prostate tissue. The over-expression of L7a and L37 mRNA was confirmed in prostate-cancer tissue samples by in situ hybridization. Elevated cancer-related expression of L4 and L30 has not been reported, but levels of the other ribosomal proteins are known to be increased in several types of cancers. These results therefore suggest that prostate cancer is comparable with other types of cancers, in that a larger pool of some ribosomal proteins is gained during the transformation process, by an unknown mechanism.

  11. Multiple case study analysis of young women's experiences in high school engineering

    Science.gov (United States)

    Pollock, Meagan C.

    richly describe the diversity of experiences. A multiple case study analysis, this study answers the question: How do gender, class, race, and other components of intersectionality, influence high school females' experiences in engineering? Nine young women taking a high school engineering course in a suburban high school in Central Texas during the school year 2011-2012 volunteered to participate. The students were observed in their engineering classes for half of the spring 2012 semester, with bi-weekly interviews with the students, monthly interviews with the teacher, and a single interview with a parent of each volunteer. The nine rich case studies provide us with new stories that help prevent us from narrowing the experiences of women to a single incomplete stereotype, because these young women vary across race, socioeconomic backgrounds, and sexual orientation. Although each story is unique, there are commonalities among their experiences, including family, influence, classroom environment, biases, and beliefs. By drawing from their collective experiences in high school engineering, the findings direct us toward recommendations for educators, parents, engineering curriculum developers, designers of teacher professional development, and future research to improve equity and access for every student in engineering.

  12. Studying abroad: a multiple case study of nursing students' international experiences.

    Science.gov (United States)

    Green, Barbara F; Johansson, Inez; Rosser, Megan; Tengnah, Cassam; Segrott, Jeremy

    2008-11-01

    This paper examines the experiences of nursing students undertaking an international placement during their pre-registration education. The study took place in two schools--one in the United Kingdom, and one in Sweden. The move of nursing education into higher education enabled students to participate in international exchange programmes. Previous research demonstrates that students participating in such programmes may gain enhanced cultural awareness and experience personal and professional growth. The study comprised a multiple case study, utilising semi-structured individual and group interviews and documentary analysis. Eighteen students from the UK and 14 from Sweden participated. Participants described an increase in confidence, self-reliance and professional knowledge and skills resulting from their international placement. There was an awareness of how healthcare roles differ between countries and a change in attitudes to others from different backgrounds and cultures. The differences between the two cases were marginal. Whilst there was support from both home and host universities this varied between the international placement providers. The international placements were beneficial; however, there is a need for change in the preparation, support and monitoring of students, greater engagement with the partner institutions, and more effective mentoring of staff.

  13. Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Michael T. Shaw

    2017-06-01

    Full Text Available BackgroundAdverse childhood experiences (ACEs exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood.ObjectiveTo investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS.MethodsSixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation.ResultsAdverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = –0.30, p = 0.04. ACEs were also linked to reading recognition (a proxy for premorbid IQ (r = –0.25, p = 0.04. ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT.ConclusionChildhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.

  14. Mass hierarchy sensitivity of medium baseline reactor neutrino experiments with multiple detectors

    Directory of Open Access Journals (Sweden)

    Hong-Xin Wang

    2017-05-01

    Full Text Available We report the neutrino mass hierarchy (MH determination of medium baseline reactor neutrino experiments with multiple detectors, where the sensitivity of measuring the MH can be significantly improved by adding a near detector. Then the impact of the baseline and target mass of the near detector on the combined MH sensitivity has been studied thoroughly. The optimal selections of the baseline and target mass of the near detector are ∼12.5 km and ∼4 kton respectively for a far detector with the target mass of 20 kton and the baseline of 52.5 km. As typical examples of future medium baseline reactor neutrino experiments, the optimal location and target mass of the near detector are selected for the specific configurations of JUNO and RENO-50. Finally, we discuss distinct effects of the reactor antineutrino energy spectrum uncertainty for setups of a single detector and double detectors, which indicate that the spectrum uncertainty can be well constrained in the presence of the near detector.

  15. Mass hierarchy sensitivity of medium baseline reactor neutrino experiments with multiple detectors

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Xin, E-mail: hxwang@iphy.me [Department of Physics, Nanjing University, Nanjing 210093 (China); Zhan, Liang; Li, Yu-Feng; Cao, Guo-Fu [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Chen, Shen-Jian [Department of Physics, Nanjing University, Nanjing 210093 (China)

    2017-05-15

    We report the neutrino mass hierarchy (MH) determination of medium baseline reactor neutrino experiments with multiple detectors, where the sensitivity of measuring the MH can be significantly improved by adding a near detector. Then the impact of the baseline and target mass of the near detector on the combined MH sensitivity has been studied thoroughly. The optimal selections of the baseline and target mass of the near detector are ∼12.5 km and ∼4 kton respectively for a far detector with the target mass of 20 kton and the baseline of 52.5 km. As typical examples of future medium baseline reactor neutrino experiments, the optimal location and target mass of the near detector are selected for the specific configurations of JUNO and RENO-50. Finally, we discuss distinct effects of the reactor antineutrino energy spectrum uncertainty for setups of a single detector and double detectors, which indicate that the spectrum uncertainty can be well constrained in the presence of the near detector.

  16. Does Educator Training or Experience Affect the Quality of Multiple-Choice Questions?

    Science.gov (United States)

    Webb, Emily M; Phuong, Jonathan S; Naeger, David M

    2015-10-01

    Physicians receive little training on proper multiple-choice question (MCQ) writing methods. Well-constructed MCQs follow rules, which ensure that a question tests what it is intended to test. Questions that break these are described as "flawed." We examined whether the prevalence of flawed questions differed significantly between those with or without prior training in question writing and between those with different levels of educator experience. We assessed 200 unedited MCQs from a question bank for our senior medical student radiology elective: an equal number of questions (50) were written by faculty with previous training in MCQ writing, other faculty, residents, and medical students. Questions were scored independently by two readers for the presence of 11 distinct flaws described in the literature. Questions written by faculty with MCQ writing training had significantly fewer errors: mean 0.4 errors per question compared to a mean of 1.5-1.7 errors per question for the other groups (P Educator experience alone had no effect on the frequency of flaws; faculty without dedicated training, residents, and students performed similarly. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

  17. An exploration of the lived experiences of individuals with relapsed multiple myeloma.

    LENUS (Irish Health Repository)

    Maher, K

    2012-02-01

    The experience of living with relapsed Multiple Myeloma (myeloma) for eight patients accessing treatment within a haematology unit in a large London hospital is explored in this study. Myeloma is recognised as incurable and is sometimes described as an \\'incurable chronic disease\\' with a main treatment option of chemotherapy. Hermeneutic phenomenology was the methodology used in conducting the study and data were collected through open-ended, unstructured interviews. Findings suggest that living with relapsed myeloma in the context of a chronic illness causes an ever-shifting perspective between illness and wellness consequently maintaining a state of uncertainty. The patients in this study placed importance on the emotional aspect of their experience. Hope, intuitive knowing and a fighting spirit were expressed as required positive elements that enabled living with relapsed myeloma. These assisted in maintaining normality, coping with bad news and adjusting to the illness. Pervading through the themes was the need to control uncertainty. Having strong support from significant others provided something to live for and the necessary social support required to promote a new orientation to life.

  18. Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders.

    Science.gov (United States)

    Büssing, Arndt; Wirth, Anne Gritli; Reiser, Franz; Zahn, Anne; Humbroich, Knut; Gerbershagen, Kathrin; Schimrigk, Sebastian; Haupts, Michael; Hvidt, Niels Christian; Baumann, Klaus

    2014-04-30

    Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 ± 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Among participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F = 9.2; p = .003) and Beauty in Life (F = 6.0; p = .015) were experienced significantly more often by women than men. However, the experience of Awe did not differ between women and men (F = 2.2; n.s.). In contrast to our hypothesis, Gratitude/Awe cannot explain any relevant variance in patients' life satisfaction (R2 = .04). Regression analyses (R2 = .42) revealed that Gratitude/Awe can be predicted best by a person's engagement in religious practices, followed by other forms of spiritual practices and life satisfaction. Female gender was a weak predictor and underlying disease showed no effect. Gratitude/Awe could be regarded as a life orientation towards noticing and appreciating the positive in life--despite the symptoms of disease. Positive spirituality/religiosity seems

  19. Identification of a secreted casein kinase 1 in Leishmania donovani: effect of protein over expression on parasite growth and virulence.

    Directory of Open Access Journals (Sweden)

    Mary Dan-Goor

    Full Text Available Casein kinase 1 (CK1 plays an important role in eukaryotic signaling pathways, and their substrates include key regulatory proteins involved in cell differentiation, proliferation and chromosome segregation. The Leishmania genome encodes six potential CK1 isoforms, of which five have orthologs in other trypanosomatidae. Leishmania donovani CK1 isoform 4 (Ldck1.4, orthologous to LmjF27.1780 is unique to Leishmania and contains a putative secretion signal peptide. The full-length gene and three shorter constructs were cloned and expressed in E. coli as His-tag proteins. Only the full-length 62.3 kDa protein showed protein kinase activity indicating that the N-terminal and C-terminal domains are essential for protein activity. LdCK1.4-FLAG was stably over expressed in L. donovani, and shown by immunofluorescence to be localized primarily in the cytosol. Western blotting using anti-FLAG and anti-CK1.4 antibodies showed that this CK1 isoform is expressed and secreted by promastigotes. Over expression of LdCK1.4 had a significant effect on promastigote growth in culture with these parasites growing to higher cell densities than the control parasites (wild-type or Ld:luciferase, P<0.001. Analysis by flow cytometry showed a higher percentage, ∼4-5-fold, of virulent metacyclic promastigotes on day 3 among the LdCK1.4 parasites. Finally, parasites over expressing LdCK1.4 gave significantly higher infections of mouse peritoneal macrophages compared to wild-type parasites, 28.6% versus 6.3%, respectively (p = 0.0005. These results suggest that LdCK1.4 plays an important role in parasite survival and virulence. Further studies are needed to validate CK1.4 as a therapeutic target in Leishmania.

  20. Over expression of vascular endothelial growth factor in correlation to Ki-67, grade and stage of breast cancer

    International Nuclear Information System (INIS)

    Al-Harris, Esraah S.; Al-Janabi, Asad A.; Al-Toriahi, Kaswer M.; Yasseen, Akeel A.

    2008-01-01

    Objective was to assess the significance of vascular endothelial growth factor (VEGF) protein over expression in human breast cancer, and its possible correlation with cell proliferation marker (Ki-67), grade and stage of breast cancer. We carried out this study at the Department of Pathology, Kufa University, between November 2006 and September 2007. A retrospective study was employed on paraffin-embedded blocks from 52 female patients with breast cancer. A group of 21 patients with benign breast lesions was included for comparison and 14 cases of normal breast tissue as control group. The investigation designed to employ immunohistochemistry using Avidin-Biotin Complex (ABC) method for detection of both VEGF and Ki-67. A total of 87 samples were included. Vascular endothelial growth factor immunoexpression was considered as positive in 61.5% of malignant and in 19% of benign breast lesions. No over expression sign has been noticed in normal breast tissue (p<0.005). No significant difference in VEGF over expression among different histological types of breast cancer (p<0.05). Vascular endothelial growth factor immunostaining was positively correlated with Ki-67, grade, stage, lymph node metastasis, and recurrence of breast cancer (p<0.05).No such correlation has been seen when the age of the patients has been considered. Vascular endothelial growth factor plays an important role in the pathogenesis of breast cancer evolution and supports the evidence of its role in angiogenesis and cell survival. This study recommended that the blocking of VEGF may be target for blocking angiogenesis and hence improving the efficacy of anti-cancer therapy. (author)

  1. Altered Fruit and Seed Development of Transgenic Rapeseed (Brassica napus Over-Expressing MicroRNA394.

    Directory of Open Access Journals (Sweden)

    Jian Bo Song

    Full Text Available Fruit and seed development in plants is a complex biological process mainly involved in input and biosynthesis of many storage compounds such as proteins and oils. Although the basic biochemical pathways for production of the storage metabolites in plants are well characterized, their regulatory mechanisms are not fully understood. In this study, we functionally identified rapeseed (Brassica napus miR394 with its target gene Brassica napus leaf curling responsiveness (BnLCR to dissect a role of miR394 during the fruit and seed development. Transgenic rapeseed plants over-expressing miR394 under the control of the cauliflower mosaic virus 35S promoter were generated. miR394 over-expression plants exhibited a delayed flowering time and enlarged size of plants, leaf blade, pods and seed body, but developed seeds with higher contents of protein and glucosinolates (GLS and lower levels of oil accumulation as compared to wild-type. Over-expression of miR394 altered the fatty acid (FA composition by increasing several FA species such as C16:0 and C18:0 and unsaturated species of C20:1 and C22:1 but lowering C18:3. This change was accompanied by induction of genes coding for transcription factors of FA synthesis including leafy cotyledon1 (BnLEC1, BnLEC2, and FUSCA3 (FUS3. Because the phytohormone auxin plays a crucial role in fruit development and seed patterning, the DR5-GUS reporter was used for monitoring the auxin response in Arabidopsis siliques and demonstrated that the DR5 gene was strongly expressed. These results suggest that BnmiR394 is involved in rapeseed fruit and seed development.

  2. Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in Females With Major Affective Disorders

    Directory of Open Access Journals (Sweden)

    Baohu Ji

    2015-08-01

    Research in context: Due to lack of biological markers, diagnosis and treatment of psychiatric disorders are subjective. There is utmost urgency to identify biomarkers for clinics, research, and drug development. We found that XIST and KDM5C gene expression may be used as a biological marker for diagnosis of major affective disorders in a significantly large subset of female patients from the general population. Our studies show that over-expression of XIST and some X-linked escapee genes may be a common mechanism for development of psychiatric disorders between the patients with rare genetic diseases (XXY or XXX and the general population of female psychiatric patients.

  3. Comprehensive RNA dataset of AGO2 associated RNAs in Jurkat cells following miR-21 over-expression

    Directory of Open Access Journals (Sweden)

    Claudia Carissimi

    2016-06-01

    Full Text Available We set out to identify miR-21 targets in Jurkat cells using a high-throughput biochemical approach (10.1016/j.biochi.2014.09.021 [1]. Using a specific monoclonal antibody raised against AGO2, RISC complexes were immunopurified in Jurkat cells over-expressing miR-21 following lentiviral trasduction as well as in Jurkat control cells lines. A parallel immunoprecipitation using isotype-matched rat IgG was performed as a control. AGO2 associated mRNAs were profiled by microarray (GEO: GSE37212. AGO2 bound miRNAs were profiled by RNA-seq.

  4. Over-expression of histone H3K4 demethylase gene JMJ15 enhances salt tolerance in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yuan eShen

    2014-06-01

    Full Text Available Histone H3 lysine 4 trimethylation (H3K4me3 has been shown to be involved in stress-responsive gene expression and gene priming in plants. However, the role of H3K4me3 resetting in the processes is not clear. In this work we studied the expression and function of Arabidopsis H3K4 demethylase gene JMJ15. We show that the expression of JMJ15 was relatively low and was limited to a number of tissues during vegetative growth but was higher in young floral organs. Over-expression of the gene in gain-of-function mutants reduced the plant height with accumulation of lignin in stems, while the loss-of-function mutation did not produce any visible phenotype. The gain-of-function mutants showed enhanced salt tolerance, whereas the loss-of-function mutant was more sensitive to salt compared to the wild type. Transcriptomic analysis revealed that over-expression of JMJ15 down-regulated many genes which are preferentially marked by H3K4me3 and H3K4me2. Many of the down-regulated genes encode transcription regulators involved in stress responses. The data suggest that increased JMJ15 levels may regulate the gene expression program that enhances stress tolerance.

  5. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

    Science.gov (United States)

    Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie

    2009-06-12

    Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (Pincrease in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

  6. Over-expression of the splice variant of CONSTANS enhances the in vitro synthesis of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Abhishek Kumar

    2017-10-01

    Full Text Available Eco-friendly biosynthetic approach for silver nanoparticles production using plant extracts is an exciting advancement in bio- nanotechnology and has been successfully attempted in more than 41 plant species. However, an established model plant system for unravelling the biochemical pathways of silver nanoparticle (AgNPs production is lacking. Here we have shown in Arabidopsis thaliana a genetic model plant and in its misexpressing lines of splice variant CONSTANS (COβ for the silver nanoparticle biosynthesis in vitro. Employing the biochemical, spectroscopic, Transmission Electron Microscopy (TEM, Raman spectroscopy, Nuclear Magnetic Resonance (NMR and powder x-rays diffraction (Powder XRD methods and using selected mutants and over- expressing line of Arabidopsis thaliana involved in sugar homeostasis. Additionally, a comparative analysis of AgNPs synthesis using different transgenic lines of Arabidopsis was explored. Here we have shown that plant extract of COβ and gi-100 (mutant line of GIGANTEA showed the highest potential of nanoparticle production as comparable to Col-0 and over- expressing line of GIGANTEA (35SGi. Silver nanoparticles production in the Arabidopsis not only opens up a possibility of using molecular genetics tool to understand the biochemical pathways, but also could address the mechanism behind different shapes of AgNPs produced using plant extracts.

  7. Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction.

    Science.gov (United States)

    Park, Dongsun; Lee, Hong Jun; Joo, Seong Soo; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Lim, Inja; Matsuo, Akinori; Tooyama, Ikuo; Kim, Yun-Bae; Kim, Seung U

    2012-04-01

    A human neural stem cell (NSC) line over-expressing human choline acetyltransferase (ChAT) gene was generated and these F3.ChAT NSCs were transplanted into the brain of rat Alzheimer disease (AD) model which was induced by application of ethylcholine mustard aziridinium ion (AF64A) that specifically denatures cholinergic nerves and thereby leads to memory deficit as a salient feature of AD. Transplantation of F3.ChAT human NSCs fully recovered the learning and memory function of AF64A animals, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF). Transplanted F3.ChAT human NSCs were found to migrate to various brain regions including cerebral cortex, hippocampus, striatum and septum, and differentiated into neurons and astrocytes. The present study demonstrates that brain transplantation of human NSCs over-expressing ChAT ameliorates complex learning and memory deficits in AF64A-cholinotoxin-induced AD rat model. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1

    Directory of Open Access Journals (Sweden)

    Eadie Brennan D

    2009-02-01

    Full Text Available Abstract Background Cognitive deficits are a hallmark feature of both Down Syndrome (DS and Alzheimer's Disease (AD. Extra copies of the genes on chromosome 21 may also play an important role in the accelerated onset of AD in DS individuals. Growing evidence suggests an important function for cholesterol in the pathogenesis of AD, particularly in APP metabolism and production of Aβ peptides. The ATP-Binding Cassette-G1 (ABCG1 transporter is located on chromosome 21, and participates in the maintenance of tissue cholesterol homeostasis. Results To assess the role of ABCG1 in DS-related cognition, we evaluated the cognitive performance of mice selectively over-expressing the ABCG1 gene from its endogenous regulatory signals. Both wild-type and ABCG1 transgenic mice performed equivalently on several behavioral tests, including measures of anxiety, as well as on reference and working memory tasks. No deficits in hippocampal CA1 synaptic plasticity as determined with electrophysiological studies were apparent in mice over-expressing ABCG1. Conclusion These findings indicate that although ABCG1 may play a role in maintaining cellular or tissue cholesterol homeostasis, it is unlikely that excess ABCG1 expression contributes to the cognitive deficits in DS individuals.

  9. Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

    Directory of Open Access Journals (Sweden)

    Hong J Lee

    Full Text Available BACKGROUND: Intracerebral hemorrhage (ICH is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

  10. Over-expression of mango (Mangifera indica L.) MiARF2 inhibits root and hypocotyl growth of Arabidopsis.

    Science.gov (United States)

    Wu, Bei; Li, Yun-He; Wu, Jian-Yong; Chen, Qi-Zhu; Huang, Xia; Chen, Yun-Feng; Huang, Xue-Lin

    2011-06-01

    An auxin response factor 2 gene, MiARF2, was cloned in our previous study [1] from the cotyledon section of mango (Mangifera indica L. cv. Zihua) during adventitious root formation, which shares an 84% amino acid sequence similarity to Arabidopsis ARF2. This study was to examine the effects of over-expression of the full-length MiARF2 open reading frame on the root and hypocotyl growth in Arabidopsis. Phenotype analysis showed that the T(3) transgenic lines had about 20-30% reduction in the length of hypocotyls and roots of the seedlings in comparison with the wild-type. The transcription levels of ANT and ARGOS genes which play a role in controlling organ size and cell proliferation in the transgenic seedlings also decreased. Therefore, the inhibited root and hypocotyl growth in the transgenic seedlings may be associated with the down-regulated transcription of ANT and ARGOS by the over-expression of MiARF2. This study also suggests that although MiARF2 only has a single DNA-binding domain (DBD), it can function as other ARF-like proteins containing complete DBD, middle region (MR) and carboxy-terminal dimerization domain (CTD).

  11. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R

    2013-01-01

    BACKGROUND: Stroke is a major cause of death and severe disability, but effective treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated as a novel pharmacological target in combating stroke and neurodegenerative disorders based on cytoprotective properties. Using...... contribution from compensatory mechanisms to the phenotype following a genetic perturbation. We also stress, that care should be taken when comparing results where different mouse strains and colonies have been used due to large genetic background contribution to the observed phenotype....

  12. MCRTOF, Multiple Scattering of Resonance Region Neutron in Time of Flight Experiments

    International Nuclear Information System (INIS)

    Ohkubo, Mako

    1984-01-01

    1 - Description of program or function: Multiple scattering of neutrons in the resonance energy region impinging on a disk with an arbitrary angle. 2 - Method of solution: The Monte Carlo method is employed to simulate the path of an incident neutron in a medium for which macroscopic cross sections are determined by resonance parameters. By tracing a large number of neutrons, probabilities for capture, transmission, front-face scattering, rear-face scattering and side-face scattering are determined and printed out as function of incident neutron energy. Optionally, the distribution of capture locations in the disk can be printed. The incident neutron energy is swept to fit a situation as encountered in time-of-flight experiments. 3 - Restrictions on the complexity of the problem: The cross section file is constructed from input resonance parameters with a single- level Breit-Wigner formula. The following restrictions and simplifications apply: - The maximum number of resonances is five. - Reactions other than capture and scattering are neglected. - The angular scattering distribution in the center-of-mass system is assumed to be uniform. - Chemical binding effects are neglected

  13. The cost and benefits of employment: a qualitative study of experiences of persons with multiple sclerosis.

    Science.gov (United States)

    Johnson, Kurt L; Yorkston, Kathryn M; Klasner, Estelle R; Kuehn, Carrie M; Johnson, Erica; Amtmann, Dagmar

    2004-02-01

    To attain a better understanding of the benefits and barriers faced by persons with multiple sclerosis (MS) in the workplace. Qualitative research methodology comprising a series of semistructured interviews. Community-based setting. Fourteen women and 2 men with MS living in the community who were employed or recently employed at the time of interviews. Not applicable. Accounts of personal experiences related to employment. Four themes emerged: the cost-benefit economy of working; fatigue and cognitive changes; stress in the workplace; and accommodations made to address barriers. Although participants valued work highly, they were also aware of the cost of being employed. The consequences of unemployment or changing jobs were considered negative and appeared stressful. For persons with MS, employment had both costs and significant benefits. Accommodations in the workplace and modifications of roles and responsibilities at home made it possible for individuals to continue working. Health care providers must consider the complexity and timing of decisions by people with MS to continue or leave employment before recommending either action. Identifying critical periods of intervention to stabilize this cost-benefit balance is a critical next step for understanding issues of employment and MS.

  14. Gender as a differential indicator of the employment discrimination experiences of Americans with multiple sclerosis.

    Science.gov (United States)

    Rumrill, Phillip D; Roessler, Richard T; McMahon, Brian T; Hennessey, Mary L; Neath, Jeanne

    2007-01-01

    Information from the Integrated Mission System of the United States Equal Employment Opportunity Commission (EEOC) was used to investigate the employment discrimination experiences of women and men with multiple sclerosis (MS). Spanning the years 1992 to 2003, the EEOC database included 3,663 allegations of discrimination filed by 2,167 adults with MS. With respect to women and men with MS, the researchers examined the comparability of a) demographic characteristics; b) industry designations, locations, and size of employers; c) the nature of discrimination alleged; and d) the legal outcome or resolution of those allegations. On average, women and men with MS were in their early forties, with the majority of both groups being Caucasian. Both women and men were most likely to allege discrimination related to discharge and reasonable accommodations, although women were more likely to file harassment charges than men. Men with MS were more likely to allege discrimination regarding hiring and reinstatement. Women with MS were more likely to file allegations against employers in the service industries, and men were more likely to file allegations against employers in the construction, manufacturing, and wholesale industries. No gender differences were found in the geographic distribution of allegations. Both groups had comparable rates of merit closures (23% vs. 27%) as a result of the EEOC's investigatory process. Implications for rehabilitation counseling and employer-oriented interventions are discussed.

  15. Pilates for people with multiple sclerosis who use a wheelchair: feasibility, efficacy and participant experiences.

    Science.gov (United States)

    van der Linden, Marietta L; Bulley, Catherine; Geneen, Louise J; Hooper, Julie E; Cowan, Paula; Mercer, Thomas H

    2014-01-01

    This mixed methods study aimed to explore the feasibility, efficacy and the participants' experiences of a Pilates programme for people with Multiple Sclerosis (pwMS) who use a wheelchair. Fifteen pwMS took part in the 12-week Pilates programme. At baseline and after 6 and 12 weeks of the programme, sitting stability, measured as maximum progression of the Centre of Pressure when leaning sideways (COPmax), posture, pain on a Visual Analogue Scale, function, fatigue and the impact of MS (MSIS29) were assessed. Ten participants took part in two focus groups within six weeks of the completion of the programme. Significant improvements at the 12-week assessment were found in COPmax (p = 0.046), sitting posture (p = 0.004), pain in the shoulders (p = 0.005) and back (p = 0.005) and MSIS29 (p = 0.006). The majority of participants described various physical, functional, psychological and social benefits from participation that reflected increased confidence in activities of daily living. Enjoyment of the classes was expressed by all, and most wished to continue participation. Pilates appears to be efficacious in improving sitting stability and posture and decreasing pain and was also well tolerated by wheelchair users with MS. Further mixed methods studies are warranted.

  16. Preservation of Multiple Mammalian Tissues to Maximize Science Return from Ground Based and Spaceflight Experiments.

    Science.gov (United States)

    Choi, Sungshin; Ray, Hami E; Lai, San-Huei; Alwood, Joshua S; Globus, Ruth K

    2016-01-01

    Even with recent scientific advancements, challenges posed by limited resources and capabilities at the time of sample dissection continue to limit the collection of high quality tissues from experiments that can be conducted only infrequently and at high cost, such as in space. The resources and time it takes to harvest tissues post-euthanasia, and the methods and duration of long duration storage, potentially have negative impacts on sample quantity and quality, thereby limiting the scientific outcome that can be achieved. The goals of this study were to optimize methods for both sample recovery and science return from rodent experiments, with possible relevance to both ground based and spaceflight studies. The first objective was to determine the impacts of tissue harvest time post-euthanasia, preservation methods, and storage duration, focusing on RNA quality and enzyme activities in liver and spleen as indices of sample quality. The second objective was to develop methods that will maximize science return by dissecting multiple tissues after long duration storage in situ at -80°C. Tissues of C57Bl/6J mice were dissected and preserved at various time points post-euthanasia and stored at -80°C for up to 11 months. In some experiments, tissues were recovered from frozen carcasses which had been stored at -80°C up to 7 months. RNA quantity and quality was assessed by measuring RNA Integrity Number (RIN) values using an Agilent Bioanalyzer. Additionally, the quality of tissues was assessed by measuring activities of hepatic enzymes (catalase, glutathione reductase and GAPDH). Fresh tissues were collected up to one hour post-euthanasia, and stored up to 11 months at -80°C, with minimal adverse effects on the RNA quality of either livers or RNAlater-preserved spleens. Liver enzyme activities were similar to those of positive controls, with no significant effect observed at any time point. Tissues dissected from frozen carcasses that had been stored for up to 7

  17. Living with uncertainty and hope: A qualitative study exploring parents' experiences of living with childhood multiple sclerosis.

    Science.gov (United States)

    Hinton, Denise; Kirk, Susan

    2017-06-01

    Background There is growing recognition that multiple sclerosis is a possible, albeit uncommon, diagnosis in childhood. However, very little is known about the experiences of families living with childhood multiple sclerosis and this is the first study to explore this in depth. Objective Our objective was to explore the experiences of parents of children with multiple sclerosis. Methods Qualitative in-depth interviews with 31 parents using a grounded theory approach were conducted. Parents were sampled and recruited via health service and voluntary sector organisations in the United Kingdom. Results Parents' accounts of life with childhood multiple sclerosis were dominated by feelings of uncertainty associated with four sources; diagnostic uncertainty, daily uncertainty, interaction uncertainty and future uncertainty. Parents attempted to manage these uncertainties using specific strategies, which could in turn create further uncertainties about their child's illness. However, over time, ongoing uncertainty appeared to give parents hope for their child's future with multiple sclerosis. Conclusion Illness-related uncertainties appear to play a role in generating hope among parents of a child with multiple sclerosis. However, this may lead parents to avoid sources of information and support that threatens their fragile optimism. Professionals need to be sensitive to the role hope plays in supporting parental coping with childhood multiple sclerosis.

  18. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles

    DEFF Research Database (Denmark)

    Hojman, Pernille; Brolin, Camilla; Gissel, Hanne

    2009-01-01

    patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (Pobese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet,) 21.9+/-1.4 g (EPO, normal diet), 35.......3+/-3.3 g (control, high-fat diet) and 28.8+/-2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance......-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles....

  19. Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice

    DEFF Research Database (Denmark)

    Brandt, Claus; Hansen, Rasmus Hvass; Hansen, Jakob Bondo

    2015-01-01

    -fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were......OBJECTIVE: Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling....../glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24h fasting. CONCLUSION: Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content....

  20. TOX3 (TNRC9) Over Expression in Bladder Cancer Cells Decreases Cellular Proliferation and Triggers an Interferon-Like Response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Mansilla Castaño, Francisco; Dyrskjøt, Lars

    2013-01-01

    Background: Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+ dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells over expressing TOX3 followed by Pathway analysis showed that TOX3 Overexpression mainly affected the Interferon Signaling Pathway. TOX3 up regulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 over...

  1. Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

    Science.gov (United States)

    Schmitt, Ulrich; Hiemke, Christoph; Fahrenholz, Falk; Schroeder, Anja

    2006-12-15

    Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

  2. Characterization of a right atrial subsidiary pacemaker and acceleration of the pacing rate by HCN over-expression.

    Science.gov (United States)

    Morris, Gwilym M; D'Souza, Alicia; Dobrzynski, Halina; Lei, Ming; Choudhury, Moinuddin; Billeter, Rudi; Kryukova, Yelena; Robinson, Richard B; Kingston, Paul A; Boyett, Mark R

    2013-10-01

    Although the right atrium (RA contains subsidiary atrial pacemaker (SAP) tissue that can take over from the sinoatrial node (SAN) in sick sinus syndrome (SSS), SAP tissue is bradycardic. Little is known about SAP tissue and one aim of the study was to characterize ion channel expression to obtain insight into SAP pacemaker mechanisms. A second aim was to determine whether HCN over-expression (a 'biopacemaker'-like strategy) can accelerate the pacemaker rate producing a pacemaker that is similar in nature to the SAN. SAP tissue was isolated from the rat and the leading pacemaker site was characterized. Cell size at the leading pacemaker site in the SAP was smaller than in the RA and comparable to that in the SAN. mRNA levels showed the SAP to be similar to, but distinct from, the SAN. For example, in the SAN and SAP, expression of Tbx3 and HCN1 was higher and Nav1.5 and Cx43 lower than in the RA. Organ-cultured SAP tissue beat spontaneously, but at a slower rate than the SAN. Adenovirus-mediated gene transfer of HCN2 and the chimeric protein HCN212 significantly increased the pacemaker rate of the SAP close to that of the native SAN, but HCN4 was ineffective. SAP tissue near the inferior vena cava is bradycardic, but shares characteristics with the SAN. Pacing can be accelerated by the over-expression of HCN2 or HCN212. This provides proof of concept for the use of SAP tissue as a substrate for biopacemaking in the treatment of SSS.

  3. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  4. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

    Directory of Open Access Journals (Sweden)

    Pernille Hojman

    Full Text Available Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01 in EPO transfected obese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet, 21.9+/-1.4 g (EPO, normal diet, 35.3+/-3.3 g (control, high-fat diet and 28.8+/-2.6 g (EPO, high-fat diet. Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

  5. Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Tiantian

    2010-05-01

    Full Text Available Abstract Background Telomerase is activated in oncogenesis, which confers an immortal phenotype to cancer cells. The AAA + ATPase Reptin is required for telomerase biogenesis by maintaining telomerase RNA (hTER stability and is aberrantly expressed in certain cancers. Given its role in chromatin remodeling and transcription regulation, we determined the effect of Reptin on the transcription of the telomerase reverse transcriptase (hTERT gene, a key component of the telomerase complex and its expression in gastric cancer. Results Knocking down Reptin or its partner Pontin using small interfering RNA in gastric and cervical cancer cells led to significant decreases in hTERT mRNA, but hTERT promoter activity was inhibited in only Reptin-depleted cells. Reptin interacted with the c-MYC oncoprotein and its stimulatory effect on the hTERTpromoter was significantly dependent on functional E-boxes in the promoter. Moreover, Reptin bound to the hTERT proximal promoter and the loss of the Reptin occupancy led to dissociation of c-MYC from the hTERT promoter in Reptin-depleted cells. Reptin inhibition dramatically impaired clonogenic potential of gastric cancer cells by inducing cell growtharrest and over-expression of Reptin was observed in primary gastric cancer specimens. Conclusions The hTERT gene is a direct target of Reptin, and hTERT transcription requires constitutive expression of Reptin and its cooperation with c-MYC. Thus, Reptin regulates telomerase at two different levels. This finding, together with the requirementof Reptin for the clonogenic potential of cancer cells and its over-expression in gastriccancer and other solid tumors, suggests that Reptin may be a putative therapeutic target.

  6. [Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

  7. Biochemical mechanisms of imidacloprid resistance in Nilaparvata lugens: over-expression of cytochrome P450 CYP6AY1.

    Science.gov (United States)

    Ding, Zhiping; Wen, Yucong; Yang, Baojun; Zhang, Yixi; Liu, Shuhua; Liu, Zewen; Han, Zhaojun

    2013-11-01

    Imidacloprid is a key insecticide extensively used for control of Nilaparvata lugens, and its resistance had been reported both in the laboratory selected strains and field populations. A target site mutation Y151S in two nicotinic acetylcholine receptor subunits and enhanced oxidative detoxification have been identified in the laboratory resistant strain, contributing importantly to imidacloprid resistance in N. lugens. To date, however, imidacloprid resistance in field population is primarily attributable to enhanced oxidative detoxification by over-expressed P450 monooxygenases. A resistant strain (Res), originally collected from a field population and continuously selected in laboratory with imidacloprid for more than 40 generations, had 180.8-fold resistance to imidacloprid, compared to a susceptible strain (Sus). Expression of different putative P450 genes at mRNA levels was detected and compared between Res and Sus strains, and six genes were found expressed significantly higher in Res strain than in Sus strain. CYP6AY1 was found to be the most different expressed P450 gene and its mRNA level in Res strain was 17.9 times of that in Sus strain. By expressing in E. coli cells, CYP6AY1 was found to metabolize imidacloprid efficiently with initial velocity calculated of 0.851 ± 0.073 pmol/min/pmol P450. When CYP6AY1 mRNA levels in Res strain was reduced by RNA interference, imidacloprid susceptibility was recovered. In four field populations with different resistance levels, high levels of CYP6AY1 transcript were also found. In vitro and in vivo studies provided evidences that the over-expression of CYP6AY1 was one of the key factors contributing to imidacloprid resistance in the laboratory selected strain Res, which might also be the important mechanism for imidacloprid resistance in field populations, when the target site mutation was not prevalent at present. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. The multiple mini-interview for selecting medical residents: first experience in the Middle East region.

    Science.gov (United States)

    Ahmed, Ashraf; Qayed, Khalil Ibrahim; Abdulrahman, Mahera; Tavares, Walter; Rosenfeld, Jack

    2014-08-01

    Numerous studies have shown that multiple mini-interviews (MMI) provides a standard, fair, and more reliable method for assessing applicants. This article presents the first MMI experience for selection of medical residents in the Middle East culture and an Arab country. In 2012, we started using the MMI in interviewing applicants to the residency program of Dubai Health Authority. This interview process consisted of eight, eight-minute structured interview scenarios. Applicants rotated through the stations, each with its own interviewer and scenario. They read the scenario and were requested to discuss the issues with the interviewers. Sociodemographic and station assessment data provided for each applicant were analyzed to determine whether the MMI was a reliable assessment of the non-clinical attributes in the present setting of an Arab country. One hundred and eighty-seven candidates from 27 different countries were interviewed for Dubai Residency Training Program using MMI. They were graduates of 5 medical universities within United Arab Emirates (UAE) and 60 different universities outside UAE. With this applicant's pool, a MMI with eight stations, produced absolute and relative reliability of 0.8 and 0.81, respectively. The person × station interaction contributed 63% of the variance components, the person contributed 34% of the variance components, and the station contributed 2% of the variance components. The MMI has been used in numerous universities in English speaking countries. The MMI evaluates non-clinical attributes and this study provides further evidence for its reliability but in a different country and culture. The MMI offers a fair and more reliable assessment of applicants to medical residency programs. The present data show that this assessment technique applied in a non-western country and Arab culture still produced reliable results.

  9. Unwinding after high salinity stress: Pea DNA helicase 45 over- expression in tobacco confers high salinity tolerance without affecting yield (abstract)

    International Nuclear Information System (INIS)

    Tuteja, N.

    2005-01-01

    Soil salinity is an increasing threat for agriculture and is a major factor in reducing plant productivity; therefore, it is necessary to obtain salinity-tolerant varieties. A typical characteristic of soil salinity is the induction of multiple stress- inducible genes. Some of the genes encoding osmolytes, ion channels or enzymes are able to confer salinity-tolerant phenotypes when transferred to sensitive plants. As salinity stress affects the cellular gene-expression machinery, it is evident that molecules involved in nucleic acid processing including helicases, are likely to be affected as well. DNA helicases unwind duplex DNA and are involved in replication, repair, recombination and transcription while RNA helicases unfold the secondary structures in RNA and are involved in transcription, ribosome biogenesis and translation initiation. We have earlier reported the isolation of a pea DNA helicase 45 (PDH45) that exhibits striking homology with eIF-4A (Plant J. 24:219-230,2000). Here we report that PDH45 mRNA is induced in pea seedlings in response to high salt and its over- expression driven by a constitutive CAMV-355-promoter in tobacco plants confers salinity tolerance, thus suggesting a new pathway for manipulating stress tolerance in crop plants. The T0 transgenic plants showed high-levels of PDH45 protein in normal and stress conditions, as compared to wild type (WT) plants. The T0 transgenics also showed tolerance to high salinity as tested by a leaf disc senescence assay. The T1 transgenics were able to grow to maturity and set normal viable seeds under continuous salinity stress, without any reduction in plant yield, in terms of seed weight. Measurement of Na/sup +/ ions in different parts of the plant showed higher accumulation in the old leaves and negligible in seeds of T1 transgenic lines as compared with the WT plants. The possible mechanism of salinity tolerance will be discussed. Over-expression of PDH45 provides a possible example of the

  10. Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

    Science.gov (United States)

    Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

    2014-08-01

    The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  11. Relevance of the hadronic interaction model in the interpretation of multiple muon data as detected with the MACRO experiment

    CERN Document Server

    Ambrosio, M; Aramo, C; Auriemma, G; Baldini, A; Barbarino, G C; Barish, B C; Battistoni, G; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bisi, V; Bloise, C; Bower, C; Bussino, S; Cafagna, F; Calicchio, M; Campana, D; Carboni, M; Castellano, M G; Cecchini, S; Cei, F; Chiarella, V; Coutu, S; De Benedictis, L; De Cataldo, G; Dekhissi, H; De Marzo, C; De Mitri, I; De Vincenzi, M; Di Credico, A; Erriquez, O; Favuzzi, C; Forti, C; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Grassi, M; Gray, L; Grillo, A; Guarino, F; Guarnaccia, P; Gustavino, C; Habig, A; Hanson, K; Hawthorne, A; Heinz, R; Iarocci, Enzo; Katsavounidis, E; Kearns, E T; Kyriazopoulou, S; Lamanna, E; Lane, C; Levin, D S; Lipari, P; Longley, N P; Longo, M J; Maaroufi, F; Mancarella, G; Mandrioli, G; Manzoor, S; Margiotta-Neri, A; Marini, A; Martello, D; Marzari-Chiesa, A; Mazziotta, M N; Mazzotta, C; Michael, D G; Mikheyev, S P; Miller, L; Monacelli, P; Montaruli, T; Monteno, M; Mufson, S L; Musser, J; Nicolò, D; Nolty, R; Okada, C; Orth, C; Osteria, G; Palamara, O; Patera, V; Patrizii, L; Pazzi, R; Peck, C W; Petrera, S; Pistilli, P; Popa, V; Rainó, A; Rastelli, A; Reynoldson, J; Ronga, F; Rubizzo, U; Sanzgiri, A; Satriano, C; Satta, L; Scapparone, E; Scholberg, K; Sciubba, A; Serra-Lugaresi, P; Severi, M; Sioli, M; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steinberg, R; Stone, J L; Sulak, Lawrence R; Surdo, A; Tarle, G; Togo, V; Walter, C W; Webb, R

    1999-01-01

    With the aim of discussing the effect of the possible sources of systematic uncertainties in simulation models, the analysis of multiple muon events from the MACRO experiment at Gran Sasso is reviewed. In particular, the predictions $9 from different currently available hadronic interaction models are compared. (9 refs).

  12. Relevance of the hadronic interaction model in the interpretation of multiple muon data as detected with the MACRO experiment

    International Nuclear Information System (INIS)

    Ambrosio, M.; Antolini, R.; Aramo, C.; Auriemma, G.; Baldini, A.; Barbarino, G. C.; Barish, B. C.; Battistoni, G.; Bellotti, R.; Bemporad, C.; Bernardini, P.; Bilokon, H.; Bisi, V.; Bloise, C.; Bower, C.; Bussino, S.; Cafagna, F.; Calicchio, M.; Campana, D.; Carboni, M.; Castellano, M.; Cecchini, S.; Cei, F.; Chiarella, V.; Coutu, S.; De Benedictis, L.; De Cataldo, G.; Dekhissi, H.; De Marzo, C.; De Mitri, I.; De Vincenzi, M.; Di Credico, A.; Erriquez, O.; Favuzzi, C.; Forti, C.; Fusco, P.; Giacomelli, G.; Giannini, G.; Giglietto, N.; Grassi, M.; Gray, L.; Grillo, A.; Guarino, F.; Guarnaccia, P.; Gustavino, C.; Habig, A.; Hanson, K.; Hawthorne, A.; Heinz, R.; Iarocci, E.; Katsavounidis, E.; Kearns, E.; Kyriazopoulou, S.; Lamanna, E.; Lane, C.; Levin, D. S.; Lipari, P.; Longley, N. P.; Longo, M. J.; Maaroufi, F.; Mancarella, G.; Mandrioli, G.; Manzoor, S.; Neri, A. Margiotta; Marini, A.; Martello, D.; Marzari-Chiesa, A.; Mazziotta, M. N.; Mazzotta, C.; Michael, D. G.; Mikheyev, S.; Miller, L.; Monacelli, P.; Montaruli, T.; Monteno, M.; Mufson, S.; Musser, J.; Nicolo, D.; Nolty, R.; Okada, C.; Orth, C.; Osteria, G.; Palamara, O.; Patera, V.; Patrizii, L.; Pazzi, R.; Peck, C. W.; Petrera, S.; Pistilli, P.; Popa, V.; Raino, A.; Rastelli, A.; Reynoldson, J.; Ronga, F.; Rubizzo, U.; Sanzgiri, A.; Satriano, C.; Satta, L.; Scapparone, E.; Scholberg, K.; Sciubba, A.; Serra-Lugaresi, P.; Severi, M.; Sioli, M.; Sitta, M.; Spinelli, P.; Spinetti, M.; Spurio, M.; Steinberg, R.; Stone, J. L.; Sulak, L. R.; Surdo, A.; Tarle, G.; Togo, V.; Walter, C. W.; Webb, R.

    1999-01-01

    With the aim of discussing the effect of the possible sources of systematic uncertainties in simulation models, the analysis of multiple muon events from the MACRO experiment at Gran Sasso is reviewed. In particular, the predictions from different currently available hadronic interaction models are compared

  13. A Mobile Service Oriented Multiple Object Tracking Augmented Reality Architecture for Education and Learning Experiences

    Science.gov (United States)

    Rattanarungrot, Sasithorn; White, Martin; Newbury, Paul

    2014-01-01

    This paper describes the design of our service-oriented architecture to support mobile multiple object tracking augmented reality applications applied to education and learning scenarios. The architecture is composed of a mobile multiple object tracking augmented reality client, a web service framework, and dynamic content providers. Tracking of…

  14. Pre-purchase customer experience : multiple case study of leading service providers in Norway

    OpenAIRE

    Kujala, Lisanna Carolina; Citic, Marija

    2015-01-01

    The theory of experience economy presents customer experience as a form of new economic offering and stresses the importance of customer experience for companies that are trying to differentiate from the competitors. Many service providers are increasing their focus on customer experience by putting the customer in the center of their business. This study investigates how experience centricity and customer centricity can be enhanced at prepurchase level. Nowadays, customer a...

  15. High level over-expression of different NCX isoforms in HEK293 cell lines and primary neuronal cultures is protective following oxygen glucose deprivation.

    Science.gov (United States)

    Cross, Jane L; Boulos, Sherif; Shepherd, Kate L; Craig, Amanda J; Lee, Sharon; Bakker, Anthony J; Knuckey, Neville W; Meloni, Bruno P

    2012-07-01

    In this study we have assessed sodium-calcium exchanger (NCX) protein over-expression on cell viability in primary rat cortical neuronal and HEK293 cell cultures when subjected to oxygen-glucose deprivation (OGD). In cortical neuronal cultures, NCX2 and NCX3 over-expression was achieved using adenoviral vectors, and following OGD increased neuronal survival from ≈20% for control vector treated cultures to ≈80% for both NCX isoforms. In addition, we demonstrated that NCX2 and NCX3 over-expression in cortical neuronal cultures enables neurons to maintain intracellular calcium at significantly lower levels than control vector treated cultures when exposed to high (9mM) extracellular calcium challenge. Further assessment of NCX activity during OGD was performed using HEK293 cell lines generated to over-express NCX1, NCX2 or NCX3 isoforms. While it was shown that NCX isoform expression differed considerably in the different HEK293 cell lines, high levels of NCX over-expression was associated with increased resistance to OGD. Taken together, our findings show that high levels of NCX over-expression increases neuronal and HEK293 cell survival following OGD, improves calcium management in neuronal cultures and provides additional support for NCX as a therapeutic target to reduce ischemic brain injury. Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  16. Multiple arterial grafts in coronary artery bypass grafting, Sohag University Hospital's initial experience

    Directory of Open Access Journals (Sweden)

    A.A.A. Elsayed

    2017-12-01

    Conclusions: Using multiple arterial grafts did not add a significant risk or time to the classic CABG. With accumulating evidence about better patency rate in arterial grafts, MAR is recommended especially in younger patients undergoing CABG.

  17. Effects of Smac gene over-expression on radiotherapeutic sensitivity of cervical cancer cell line HeLa

    International Nuclear Information System (INIS)

    Zheng Liduan; Wang Liang; Tong Qiangsong; Fei Shihong; Xiong Yufang; Wu Gang

    2005-01-01

    Objective: To study the effects of extrinsic Smac gene transfection and its over-expression on radiotherapeutic sensitivity of cervical cancer cells, in order to explore a novel strategy for ameliorating radiotherapy of cervical cancer. Methods: After Smac gene was transferred into cells of cervical cancer cell line HeLa, the subclone cells were obtained by persistent G 418 selection. Cellular Smac gene expression was determined by RT-PCR and Western blot. After treatment with X-ray irradiation, cellular growth activity in vitro was investigated by MTT colorimetry. Cellular apoptosis and its rate were determined by electron microscopy, Annexin V-FITC and propidium iodide staining flow cytometry. Cellular Caspase-3 protein expression and its activity were assayed by Western blot and colorimetry. Results: RT-PCR and Western blot demonstrated that Smac mRNA and protein levels of HeLa/Smac cells, the selected subclone cells of cervical cancer cell line, were significantly higher than those of HeLa cells (P<0.01). After treated with 8 Gy X-ray irradiation, growth activity of HeLa/Smac cells reduced by 10.19%(P<0.01), as compared with that of HeLa cells. Partial HeLa/Smac cancer cells presented characteristic morphological changes of apoptosis under electron microscope, with an apoptosis rate of 16.4%, which was significantly higher than that of HeLa cells(6.2%, P<0.01). Compared with HeLa cells, Caspase-3 expression level in HeLa/Smac was improved significantly (P<0.01), while its activity was 3.42 times as much as that of HeLa cells (P<0.01). Conclusion: Stable transfection of extrinsic Smac gene and its over-expression in cervical cancer cell line could significantly enhance cellular caspase-3 expression and activity, ameliorate apoptosis-inducing effects of radiation on cancer cells, which would be a novel strategy to improve radiotherapeutic effects for cervical cancer. (authors)

  18. How is brand experience designed in practice? : Results of a multiple-case study

    NARCIS (Netherlands)

    Bakker-Wu, S.; Calabretta, G.; Hultink, H.J.; Bohemia, E.; de Bont, C.; Svengren Holm, L.

    2017-01-01

    Brand experience is an important concept in marketing because it can affect brand loyalty, brand recall, and brand attitude. Brand experience design is therefore an important practice for companies to create favourable and meaningful experiences, through the design of various touchpoints that are in

  19. Over-expressed Testis-specific Protein Y-encoded 1 as a novel biomarker for male hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Shan Li

    Full Text Available Hepatocellular carcinoma (HCC is a male-predominant cancer. Previous studies have focused on the sex-related disparity in HCC, but the underlying mechanism remains unclear. Here, we aimed to discover characteristic biomarkers for male HCC. Clinical samples were subjected to iTRAQ labeling followed by 2DLC-ESI-MS/MS analysis. Seventy-three differential proteins containing 16 up-regulated and 57 down-regulated proteins were screened out in the male HCC group compared to that in female HCC group. Testis-specific Protein Y-encoded 1(TSPY1 is characteristically present in male HCC and was chosen for further investigation. The data from the functional effects of TSPY1 indicated that over-expression of TSPY1 could potentiate HCC cell proliferation, increase soft agar colonization, induce higher cell invasive ability and correlate with the metastatic potential of the HCC cell lines. In addition, TSPY1 and androgen receptor (AR were co-expressed simultaneously in HCC cell lines as well as in HCC tissue. TSPY1 up- or down-regulation could lead to a high or low level expression of AR. These results implied that TSPY1 may be included in the regulation of AR expression involved in male HCC and it may act as a novel biomarker for male HCC.

  20. Over-expression of brain-derived neurotrophic factor in mesenchymal stem cells transfected with recombinant lentivirus BDNF gene.

    Science.gov (United States)

    Zhang, X; Zhu, J; Zhang, K; Liu, T; Zhang, Z

    2016-12-30

    This study was aimed at investigating the expression of brain-derived neurotrophic factor (BDNF) in mesenchymal stem cells (MSCs) modified with recombinant lentivirus bearing BDNF gene. Lentivirus vectors bearing BDNF gene were constructed. MSCs were isolated from rats and cultured. The lentiviral vectors containing BDNF gene were transfected into the MSCs, and BDNF gene and protein expressions were monitored with enhanced green fluorescent protein (EGFP). RT-PCR and Western blot were used to measure gene and protein expressions, respectibvely in MSCs, MSCs-EGFP and MSCs-EGFP-BDNF groups. Green fluorescence assay confirmed successful transfection of BDNF gene recombinant lentivirus into MSCs. RT-PCR and Western blot revealed that BDNF gene and protein expressions in the MSCs-EGFP-BDNF group were significantly higher than that in MSCs group and MSCs-EGFP group. There were no statistically significant differences in gene expression between MSCs and MSCs-EGFP groups. MSCs can over-express BDNF when transfected with recombinant lentivirus bearing BDNF gene.

  1. Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

    Science.gov (United States)

    Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

    2015-01-01

    YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

  2. Over-expression of a novel JAZ family gene from Glycine soja, increases salt and alkali stress tolerance.

    Science.gov (United States)

    Zhu, Dan; Cai, Hua; Luo, Xiao; Bai, Xi; Deyholos, Michael K; Chen, Qin; Chen, Chao; Ji, Wei; Zhu, Yanming

    2012-09-21

    Salt and alkali stress are two of the main environmental factors limiting crop production. Recent discoveries show that the JAZ family encodes plant-specific genes involved in jasmonate signaling. However, there is only limited information about this gene family in abiotic stress response, and in wild soybean (Glycine soja), which is a species noted for its tolerance to alkali and salinity. Here, we isolated and characterized a novel JAZ family gene, GsJAZ2, from G. soja. Transcript abundance of GsJAZ2 increased following exposure to salt, alkali, cold and drought. Over-expression of GsJAZ2 in Arabidopsis resulted in enhanced plant tolerance to salt and alkali stress. The expression levels of some alkali stress response and stress-inducible marker genes were significantly higher in the GsJAZ2 overexpression lines as compared to wild-type plants. Subcellular localization studies using a GFP fusion protein showed that GsJAZ2 was localized to the nucleus. These results suggest that the newly isolated wild soybean GsJAZ2 is a positive regulator of plant salt and alkali stress tolerance. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons.

    Science.gov (United States)

    Shen, Yin; Zhao, Hong-Yang; Wang, Hai-Jun; Wang, Wen-Liang; Zhang, Li-Zhi; Fu, Rong

    2016-08-01

    The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

  4. Multiple myeloma and central nervous system involvement: experience of a Brazilian center

    Directory of Open Access Journals (Sweden)

    Ana Luiza Miranda Silva Dias

    2018-01-01

    Full Text Available Introduction: The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. Methods: This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Results: Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Conclusion: Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable. Keywords: Central nervous system, Multiple myeloma, Radiotherapy, Chemotherapy, Prognosis

  5. The feeling of fluent perception: a single experience from multiple asynchronous sources.

    Science.gov (United States)

    Wurtz, Pascal; Reber, Rolf; Zimmermann, Thomas D

    2008-03-01

    Zeki and co-workers recently proposed that perception can best be described as locally distributed, asynchronous processes that each create a kind of microconsciousness, which condense into an experienced percept. The present article is aimed at extending this theory to metacognitive feelings. We present evidence that perceptual fluency-the subjective feeling of ease during perceptual processing-is based on speed of processing at different stages of the perceptual process. Specifically, detection of briefly presented stimuli was influenced by figure-ground contrast, but not by symmetry (Experiment 1) or the font (Experiment 2) of the stimuli. Conversely, discrimination of these stimuli was influenced by whether they were symmetric (Experiment 1) and by the font they were presented in (Experiment 2), but not by figure-ground contrast. Both tasks however were related with the subjective experience of fluency (Experiments 1 and 2). We conclude that subjective fluency is the conscious phenomenal correlate of different processing stages in visual perception.

  6. EXQ: development and validation of a multiple-item scale for assessing customer experience quality

    OpenAIRE

    Klaus, Philipp

    2010-01-01

    Positioned in the deliberations related to service marketing, the conceptualisation of service quality, current service quality measurements, and the importance of the evolving construct of customer experience, this thesis develops and validates a measurement for customer experience quality (EXQ) in the context of repeat purchases of mortgage buyers in the United Kingdom. The thesis explores the relationship between the customer experience quality and the important marketing ou...

  7. Study and development of the data transfer for the NA50 experiment: transputer network of the multiplicity detector

    International Nuclear Information System (INIS)

    Capony, V.

    1996-01-01

    This thesis presents the works performed for the experiment NA50 at CERN, in he framework of the development of its multiplicity detector. The two first chapters describe the physical aims of the experiment and the apparatus used. The remaining part of this document shows the data readout device, developed for the multiplicity detector. Built on a T8 transputer network, this system is able to treat 8 Mbytes of data at each SPS accelerator cycle. It integrates an on-line event-builder. A filtering algorithm estimates the validity of the information and allows the flagging of all the data. The last function of this transputers network is to transfer data from the detector to the data acquisition system. Our system is able to control a data rate transfer of 35 Gbytes per day. (author)

  8. Multiple scattering effects in fast neutron polarization experiments using high-pressure helium-xenon gas scintillators as analyzers

    International Nuclear Information System (INIS)

    Tornow, W.; Mertens, G.

    1977-01-01

    In order to study multiple scattering effects both in the gas and particularly in the solid materials of high-pressure gas scintillators, two asymmetry experiments have been performed by scattering of 15.6 MeV polarized neutrons from helium contained in stainless steel vessels of different wall thicknesses. A monte Carlo computer code taking into account the polarization dependence of the differential scattering cross sections has been written to simulate the experiments and to calculate corrections for multiple scattering on helium, xenon and the gas containment materials. Besides the asymmetries for the various scattering processes involved, the code yields time-of-flight spectra of the scattered neutrons and pulse height spectra of the helium recoil nuclei in the gas scintillator. The agreement between experimental results and Monte Carlo calculations is satisfactory. (Auth.)

  9. Initial Clinical Experience in Multiple Myeloma Staging by Means of Whole-Body Resonance Techniques

    International Nuclear Information System (INIS)

    Gallego, J. I.; Concepcion, L.; Alonso, S.; Sanchez, B.; Manzi, F.

    2003-01-01

    To develop a magnetic resonance (MR) exploratory technique equivalent to serial bone X-ray, and to compare their precision in the staging of multiple myeloma (MM) patients. Multiple acquisition T1-weights TSE and STIR sequences in the coronal plane were performed. Ten healthy volunteers and 11 multiple myeloma diagnosed patients were included. The visualization of bony structures was particularly noted,with special attention given to those which would normally be included in a serial bone X-ray. In the case of the patients, a comparison was made between diagnostic capacities of the MR sequences. MR highlighters significantly more (p<0.05) bony elements than did the serial bone X-ray. This was greatly due to a sequential displacement of the scanner bed, allowing for field-of-views which were minimally from head to third proximal of the leg. Magnetic resonance detected a significantly higher number (p<0.05) of lesions. It was, in turn, capable of revealing greater lesion extensions, even to the point of implying staging classification changes in 18% of the patients. The utilization of whole-body MR techniques in multiple myeloma patients is feasible and clinically beneficial. MR is both more sensitive and more specific than serial bone X-ray for evaluation of bony lesions in MM. It is currently serving as a valid alternative in a growing numbers of patients. (Author) 10 refs

  10. Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

    Science.gov (United States)

    Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

    2011-01-01

    Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

  11. Multiple myeloma and central nervous system involvement: experience of a Brazilian center.

    Science.gov (United States)

    Dias, Ana Luiza Miranda Silva; Higashi, Fabiana; Peres, Ana Lúcia M; Cury, Pricilla; Crusoé, Edvan de Queiroz; Hungria, Vânia Tietsche de Moraes

    The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable. Copyright © 2017. Published by Elsevier Editora Ltda.

  12. Similarly Torn, Differentially Shorn? The Experience and Management of Conflict between Multiple Roles, Relationships, and Social Categories

    Directory of Open Access Journals (Sweden)

    Janelle M. Jones

    2017-10-01

    Full Text Available In three studies we examined the experience and management of conflict between different types of multiple identities. Participants described a conflict between pairs of role, relational, or social identities before rating the experience (i.e., magnitude, stress, and growth and management of conflict on a newly developed scale assessing four strategies: reconciliation, where identities are integrated, realignment, where one identity is chosen over another, retreat, where both identities are avoided, and reflection, where fit (with others, situation determines identity selection. In general, the types of identities mattered for conflict management but not its experience: Magnitude and growth did not differ, however, stress was greater for role identity conflicts (Study 3 only and participants endorsed the use of more realignment for role conflicts (Study 2 and more retreat for relational conflicts (Study 3 relative to other types of identity conflicts. Furthermore, findings suggested that the perceived flexibility of identities, not their importance or valence, were associated with realignment and retreat for roles and with retreat for relationships. Experiencing conflicts between multiple identities leaves people similarly torn, but multiple roles and relationships may be differentially shorn to manage conflict.

  13. Similarly Torn, Differentially Shorn? The Experience and Management of Conflict between Multiple Roles, Relationships, and Social Categories

    Science.gov (United States)

    Jones, Janelle M.; Hynie, Michaela

    2017-01-01

    In three studies we examined the experience and management of conflict between different types of multiple identities. Participants described a conflict between pairs of role, relational, or social identities before rating the experience (i.e., magnitude, stress, and growth) and management of conflict on a newly developed scale assessing four strategies: reconciliation, where identities are integrated, realignment, where one identity is chosen over another, retreat, where both identities are avoided, and reflection, where fit (with others, situation) determines identity selection. In general, the types of identities mattered for conflict management but not its experience: Magnitude and growth did not differ, however, stress was greater for role identity conflicts (Study 3 only) and participants endorsed the use of more realignment for role conflicts (Study 2) and more retreat for relational conflicts (Study 3) relative to other types of identity conflicts. Furthermore, findings suggested that the perceived flexibility of identities, not their importance or valence, were associated with realignment and retreat for roles and with retreat for relationships. Experiencing conflicts between multiple identities leaves people similarly torn, but multiple roles and relationships may be differentially shorn to manage conflict. PMID:29051744

  14. Similarly Torn, Differentially Shorn? The Experience and Management of Conflict between Multiple Roles, Relationships, and Social Categories.

    Science.gov (United States)

    Jones, Janelle M; Hynie, Michaela

    2017-01-01

    In three studies we examined the experience and management of conflict between different types of multiple identities. Participants described a conflict between pairs of role, relational, or social identities before rating the experience (i.e., magnitude, stress, and growth) and management of conflict on a newly developed scale assessing four strategies: reconciliation , where identities are integrated, realignment , where one identity is chosen over another, retreat , where both identities are avoided, and reflection , where fit (with others, situation) determines identity selection. In general, the types of identities mattered for conflict management but not its experience: Magnitude and growth did not differ, however, stress was greater for role identity conflicts ( Study 3 only ) and participants endorsed the use of more realignment for role conflicts ( Study 2 ) and more retreat for relational conflicts ( Study 3 ) relative to other types of identity conflicts. Furthermore, findings suggested that the perceived flexibility of identities, not their importance or valence, were associated with realignment and retreat for roles and with retreat for relationships. Experiencing conflicts between multiple identities leaves people similarly torn, but multiple roles and relationships may be differentially shorn to manage conflict.

  15. Gain-of-function analysis of poplar CLE genes in Arabidopsis by exogenous application and over-expression assays.

    Science.gov (United States)

    Liu, Yisen; Yang, Shaohui; Song, Yingjin; Men, Shuzhen; Wang, Jiehua

    2016-04-01

    Among 50 CLE gene family members in the Populus trichocarpa genome, three and six PtCLE genes encode a CLE motif sequence highly homologous to Arabidopsis CLV3 and TDIF peptides, respectively, which potentially make them functional equivalents. To test and compare their biological activity, we first chemically synthesized each dodecapeptide and analysed itsi n vitro bioactivity on Arabidopsis seedlings. Similarly, but to a different extent, three types of poplar CLV3-related peptides caused root meristem consumption, phyllotaxis disorder, anthocyanin accumulation and failure to enter the bolting stage. In comparison, application of two poplar TDIF-related peptides led to root length promotion in a dose-dependent manner with an even stronger effect observed for poplar TDIF-like peptide than TDIF. Next, we constructed CaMV35S:PtCLE transgenic plants for each of the nine PtCLE genes. Phenotypic abnormalities exemplified by arrested shoot apical meristem and abnormal flower structure were found to be more dominant and severe in 35S:PtCLV3 and 35S:PtCLV3-like2 lines than in the 35S:PtCLV3-like line. Disordered vasculature was detected in both stem and hypocotyl cross-sections in Arabidopsis plants over-expressing poplar TDIF-related genes with the most defective vascular patterning observed for TDIF2 and two TDIF-like genes. Phenotypic difference consistently observed in peptide application assay and transgenic analysis indicated the functional diversity of nine poplar PtCLE genes under investigation. This work represents the first report on the functional analysis of CLE genes in a tree species and constitutes a basis for further study of the CLE peptide signalling pathway in tree development. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Over-expression of CXCR4, a stemness enhancer, in human blastocysts by low level laser irradiation

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Tahmasbi

    2013-09-01

    Full Text Available The key role of chemokine receptor CXCR4 in the maintenance of stemness property of stem cells has been shown recently. The low level laser irradiation (LLLI is being used currently in a wide variety of clinical cases as a therapeutic tool for wound healing, relieving pain and destroying tumor cells. The aim of this study was to evaluate the effect of LLLI mimicking low level laser therapy (LLLT on the expression level of CXCR4 gene a few hours after irradiation on human blastocysts. After the development of human embryos to the first grade blastocyst stage, they were irradiated with a low power Ga-Al-As laser at a continuous wavelength of 650 nm and a power output of 30 mW. The total RNA of the irradiated blastocysts and control groups were isolated in groups of 1x2 J/cm2, 2x2 J/cm2, 1x4 J/cm2 and 2x4 J/cm2 LLLI. Specific Real-Time PCR primers were designed to amplify all the two CXCR4 isoforms yet identified. RNA amplifications were done for all the groups. We showed for the first time that LLLI makes the human blastocysts to increase the expression level of CXCR4 a few hours after irradiation. Moreover, it was shown that two irradiation doses with one day interval can cause a significant increase in CXCR4 expression level in human blastocysts. This study revealed that LLLI could be a proliferation motivator for embryonic cell divisions through enhanced over-expression of CXCR4 level.

  17. Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

    Science.gov (United States)

    Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

    2014-01-01

    Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Over-expression of a novel JAZ family gene from Glycine soja, increases salt and alkali stress tolerance

    International Nuclear Information System (INIS)

    Zhu, Dan; Cai, Hua; Luo, Xiao; Bai, Xi; Deyholos, Michael K.; Chen, Qin; Chen, Chao; Ji, Wei; Zhu, Yanming

    2012-01-01

    Highlights: ► We isolated and characterized a novel JAZ family gene, GsJAZ2, from Glycine soja. ► Overexpression of GsJAZ2 enhanced plant tolerance to salt and alkali stress. ► The transcriptions of stress marker genes were higher in GsJAZ2 overexpression lines. ► GsJAZ2 was localized to nucleus. -- Abstract: Salt and alkali stress are two of the main environmental factors limiting crop production. Recent discoveries show that the JAZ family encodes plant-specific genes involved in jasmonate signaling. However, there is only limited information about this gene family in abiotic stress response, and in wild soybean (Glycine soja), which is a species noted for its tolerance to alkali and salinity. Here, we isolated and characterized a novel JAZ family gene, GsJAZ2, from G. soja. Transcript abundance of GsJAZ2 increased following exposure to salt, alkali, cold and drought. Over-expression of GsJAZ2 in Arabidopsis resulted in enhanced plant tolerance to salt and alkali stress. The expression levels of some alkali stress response and stress-inducible marker genes were significantly higher in the GsJAZ2 overexpression lines as compared to wild-type plants. Subcellular localization studies using a GFP fusion protein showed that GsJAZ2 was localized to the nucleus. These results suggest that the newly isolated wild soybean GsJAZ2 is a positive regulator of plant salt and alkali stress tolerance.

  19. RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation.

    Science.gov (United States)

    Wu, Nan; Ren, Dong; Li, Su; Ma, Wenli; Hu, Shaoyan; Jin, Yan; Xiao, Sheng

    2018-01-10

    Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays. Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs. RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response.

  20. Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock.

    Science.gov (United States)

    Collin, Solène; Sennoun, Nacira; Dron, Anne-Gaëlle; de la Bourdonnaye, Mathilde; Montemont, Chantal; Asfar, Pierre; Lacolley, Patrick; Meziani, Ferhat; Levy, Bruno

    2011-05-01

    To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular K(ATP) (PNU-37883A) or BK(Ca) [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular K(ATP) channels, while expression of vascular BK(Ca) channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular K(ATP) channel expression. Vascular K(ATP) but not BK(Ca) channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular K(ATP) channel inhibitors offer potential therapeutic perspectives for septic shock.

  1. Over-expression of gene encoding heat shock protein 70 from Mycobacterium tuberculosis and its evaluation as vaccine adjuvant

    Directory of Open Access Journals (Sweden)

    J Dhakal

    2013-01-01

    Full Text Available Background: Heat shock proteins (Hsps are evolutionary ancient and highly conserved molecular chaperons found in prokaryotes as well as eukaryotes. Hsp70 is a predominant member of Hsp family. Microbial Hsp70s (mHsp70s have acquired special significance in immunity since they have been shown to be potent activators of the innate immune system and generate specific immune responses against tumours and infectious agents. Objectives: The present study was aimed to clone express and purify recombinant Hsp70 from the Mycobacterium tuberculosis and characterise it immunologically. The study also aimed at determining the potential of recombinant M. tuberculosis heat shock protein (rMTB-Hsp70 as adjuvant or antigen carrier. Materials and Methods: Cloning of M. tuberculosis heat shock protein (MTB-Hsp70 amplicon was carried out using the pGEMT-Easy vector although for expression, pProExHTb prokaryotic expression vector was used. Purification of recombinant Hsp70 was carried out by nickel-nitrilotriacetic acid (Ni-NTA affinity chromatography. For immunological characterization and determining the adjuvant effect of MTB-Hsp70, BALB/c mice were used. The data obtained was statistically analysed. Results: Hsp70 gene was cloned, sequenced and the sequence data were submitted to National Center for Biotechnology Information (NCBI. Recombinant MTB-Hsp70 was successfully over-expressed using the prokaryotic expression system and purified to homogeneity. The protein was found to be immunodominant. Significant adjuvant effect was produced by the rMTB-Hsp70 when inoculated with recombinant outer membrane protein 31; however, effect was less than the conventionally used the Freund′s adjuvant. Conclusion: Protocol standardised can be followed for bulk production of rHsp70 in a cost-effective manner. Significant adjuvant effect was produced by rMTB-Hsp70; however, the effect was than Freund′s adjuvant. Further, studies need to be carried out to explore its

  2. An array of Escherichia coli clones over-expressing essential proteins: A new strategy of identifying cellular targets of potent antibacterial compounds

    International Nuclear Information System (INIS)

    Xu, H. Howard; Real, Lilian; Bailey, Melissa Wu

    2006-01-01

    With the advancement of high throughput screening, it has become easier and faster to discover hit compounds that inhibit proliferation of bacterial cells. However, development in technologies used to identify cellular targets of potent antibacterial inhibitors has lagged behind. Here, we describe a novel strategy of target identification for antibacterial inhibitors using an array of Escherichia coli clones each over-expressing one essential protein. In a proof-of-concept study, eight essential genes were cloned into pLex5BA vector under the control of an inducible promoter. Over-expression of target proteins was confirmed. For two clones, one over-expressing FabI and the other over-expressing MurA enzymes, the host cells became 17- and 139-fold more resistant to the specific inhibitors triclosan and phosphomycin, respectively, while the susceptibility of other clones towards these inhibitors remained unchanged after induction of gene expression. Target identification via target protein over-expression was demonstrated using both mixed clone and individual clone assay formats

  3. Do Students Behave Rationally in Multiple Choice Tests? Evidence from a Field Experiment

    OpenAIRE

    María Paz Espinosa; Javier Gardeazabal

    2013-01-01

    A disadvantage of multiple choice tests is that students have incentives to guess. To discourage guessing, it is common to use scoring rules that either penalize wrong answers or reward omissions. In psychometrics, penalty and reward scoring rules are considered equivalent. However, experimental evidence indicates that students behave differently under penalty or reward scoring rules. These differences have been attributed to the different framing (penalty versus reward). In this paper, we mo...

  4. Coordinated voltage control for multiple wind plants in Eastern Wyoming. Analysis, field experience and validation

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Nicholas; MacDowell, Jason; Chmiel, Gary; Konopinski, Ryan; Gautam, Durga [GE Energy, Schenectady, NY (United States); Laughter, Grant; Hagen, Dave [PacifiCorp., Salt Lake City, UT (United States)

    2012-07-01

    At high levels of wind power penetration, multiple wind plants may be the predominant generation resource over large geographic areas. Thus, not only do wind plants need to provide a high level of functionality, they must coordinate properly with each other. This paper describes the analysis and field testing of wind plant voltage controllers designed to improve system voltage performance through passive coordination. The described wind power plant controls can coordinate the real and reactive power response of multiple wind turbines and thereby make the plant function as a single ''grid friendly'' power generation source. For this application, involving seven large wind plants with predominantly GE wind turbines in Eastern Wyoming, the voltage portion of the controllers were configured and tuned to allow the collective reactive power response of multiple wind plants in the region to work well together. This paper presents the results of the initial configuration and tuning study, and the results of the subsequent field tuning and testing of the modified controls. The paper also presents some comparisons of the measured field performance with the stability simulation models, which show that the available wind plant models provide accurate, high fidelity results for actual operating conditions of commercial wind power plants. (orig.)

  5. Ensinando e aprendendo com portadores de Esclerose Múltipla: relato de experiência Enseñando y aprendiendo com los portatodes de Esclerósis Multiple: relato de experiencia Teaching and learning with Multiple Sclerosis patients: experience report

    Directory of Open Access Journals (Sweden)

    Lúcia Helena Rios Barbosa de Almeida

    2007-08-01

    Full Text Available Relatode experiência realizado para descrever a vivência de um grupo de estudantes de Enfermagem da Universidade Federal do Piauí, diante da realidade do ser portador de Esclerose Múltipla. A experiência evidencia a necessidade de uma equipe integrada para obter conhecimentos fundamentais e oferecer uma assistência holística ao portador. Enfatiza-se o impacto das ações desenvolvidas pelos estudantes, na Associação Piauiense de Esclerose Múltipla, possibilitando-os a conviver melhor com as dificuldades advindas com a doença. Além disso, a comunidade em geral é favorecida através dos conhecimentos repassados mediante atividades desenvolvidas pelo grupo. Concluímos que um conhecimento mais amplo acerca de uma patologia ainda tão cheia de mistérios só é possível quando se alia teoria à realidade do paciente.Este es un relato de una experiência de trabajo realizado por un grupo de estudiantes de Enfermería de la Universidad Federal de Piauí, sobre la siutación de un portador de Esclerosis Multiple. La experiencia demuestra la necesidad de un equipo integrado para obtener conocimientos fundamentales y ofrecer una asistencia integral al portador. Aquí se enfatiza las acciones desarrolladas por los estudiantes, dentro de la APPEM (Asociación Piauiense de Esclerósis Multiple, posible a coexistir mejor él las dificultades que se sucedierón con la enfermedad. Favorecen la comunidad en general con el conocimiento repasado por medio de las actividades desarrolladas para el grupo. Un conocimiento más amplio acerca de una patología llena de misterios, solo es posible, cuando se junta la teoria a la realidad del paciente.This report describes the experience of a group of nursing students from Universidad Federal do Piauí, in face of the reality of multiple sclerosis patient. The experience highlight the necessity of an integrated team to achieve fundamental knowledge and to offer a holistic assistance to the patient. The

  6. Implementation of an object oriented track reconstruction model into multiple LHC experiments*

    Science.gov (United States)

    Gaines, Irwin; Gonzalez, Saul; Qian, Sijin

    2001-10-01

    An Object Oriented (OO) model (Gaines et al., 1996; 1997; Gaines and Qian, 1998; 1999) for track reconstruction by the Kalman filtering method has been designed for high energy physics experiments at high luminosity hadron colliders. The model has been coded in the C++ programming language and has been successfully implemented into the OO computing environments of both the CMS (1994) and ATLAS (1994) experiments at the future Large Hadron Collider (LHC) at CERN. We shall report: how the OO model was adapted, with largely the same code, to different scenarios and serves the different reconstruction aims in different experiments (i.e. the level-2 trigger software for ATLAS and the offline software for CMS); how the OO model has been incorporated into different OO environments with a similar integration structure (demonstrating the ease of re-use of OO program); what are the OO model's performance, including execution time, memory usage, track finding efficiency and ghost rate, etc.; and additional physics performance based on use of the OO tracking model. We shall also mention the experience and lessons learned from the implementation of the OO model into the general OO software framework of the experiments. In summary, our practice shows that the OO technology really makes the software development and the integration issues straightforward and convenient; this may be particularly beneficial for the general non-computer-professional physicists.

  7. Experiences in simulating and testing coordinated voltage control provided by multiple wind power plants

    Energy Technology Data Exchange (ETDEWEB)

    Arlaban, T.; Alonso, O.; Ortiz, D. [Acciona Windpower S.A. (Spain); Peiro, J.; Rivas, R. [Red Electrica de Espana SAU (Spain); Quinonez-Varela, G.; Lorenzo, P. [Acciona Energia S.A. (Spain)

    2011-07-01

    This document presents some field tests performed in a transmission system node in order to check the adequacy of voltage control performance by multiple wind power plants, with an overall capacity of 395 MW. It briefly explains the Spanish TSO motivation towards new voltage control requirements and the necessity of performing such tests in order to set the most convenient voltage control parameters and to verify the stable operation. It presents how different the voltage control capability between modern wind turbines (DFIG) and older ones (SCIG) specifically retrofitted for voltage control is. (orig.)

  8. Multiple daily fractionation in radiotherapy: biological rationale and preliminary clinical experiences

    Energy Technology Data Exchange (ETDEWEB)

    Arcangeli, G [Instituto Medico Scientifico, Rome (Italy). Dept. of Oncology; Mauro, F; Morelli, D; Nervi, C

    1979-09-01

    The biological bases of radiation dose fractionation are reviewed and discussed with special emphasis on reassortment. Experimental data on animal model systems are presented to clarify that reassortment has to be added to sublethal damage repair and reoxygenation in the rationale for an optimized radiotherapy course according to tumor cell kinetics. Clinical results on several human tumors treated with twice or thrice daily fractions are described. These results show that some clinically radioresistant tumors (especially if not characterized by a relatively long clinical doubling line) can be satisfactorily dealt with using multiple daily fractionation. Clinical observations indicate that a relatively high cumulative daily dose (200 + 150 + 150 rad) can be safely administered.

  9. Cellobiohydrolase B of Aspergillus niger over-expressed in Pichia pastoris stimulates hydrolysis of oil palm empty fruit bunches.

    Science.gov (United States)

    Woon, James Sy-Keen; Mackeen, Mukram M; Illias, Rosli M; Mahadi, Nor M; Broughton, William J; Murad, Abdul Munir Abdul; Abu Bakar, Farah Diba

    2017-01-01

    Aspergillus niger , along with many other lignocellulolytic fungi, has been widely used as a commercial workhorse for cellulase production. A fungal cellulase system generally includes three major classes of enzymes i.e., β-glucosidases, endoglucanases and cellobiohydrolases. Cellobiohydrolases (CBH) are vital to the degradation of crystalline cellulose present in lignocellulosic biomass. However, A. niger naturally secretes low levels of CBH. Hence, recombinant production of A. niger CBH is desirable to increase CBH production yield and also to allow biochemical characterisation of the recombinant CBH from A. niger . In this study, the gene encoding a cellobiohydrolase B ( cbh B) from A. niger ATCC 10574 was cloned and expressed in the methylotrophic yeast Pichia pastoris X-33. The recombinant CBHB was purified and characterised to study its biochemical and kinetic characteristics. To evaluate the potential of CBHB in assisting biomass conversion, CBHB was supplemented into a commercial cellulase preparation (Cellic ® CTec2) and was used to hydrolyse oil palm empty fruit bunch (OPEFB), one of the most abundant lignocellulosic waste from the palm oil industry. To attain maximum saccharification, enzyme loadings were optimised by response surface methodology and the optimum point was validated experimentally. Hydrolysed OPEFB samples were analysed using attenuated total reflectance FTIR spectroscopy (ATR-FTIR) to screen for any compositional changes upon enzymatic treatment. Recombinant CBHB was over-expressed as a hyperglycosylated protein attached to N -glycans. CBHB was enzymatically active towards soluble substrates such as 4-methylumbelliferyl-β-D-cellobioside (MUC), p -nitrophenyl-cellobioside ( p NPC) and p -nitrophenyl-cellobiotrioside ( p NPG3) but was not active towards crystalline substrates like Avicel ® and Sigmacell cellulose. Characterisation of purified CBHB using MUC as the model substrate revealed that optimum catalysis occurred at 50 °C and

  10. Systematic analysis of gene expression pattern in has-miR-197 over-expressed human uterine leiomyoma cells.

    Science.gov (United States)

    Ling, Jing; Wu, Xiaoli; Fu, Ziyi; Tan, Jie; Xu, Qing

    2015-10-01

    Our previous study showed that the expression of miR-197 in leiomyoma was down-regulated compared with myometrium. Further, miR-197 has been identified to affect uterine leiomyoma cell proliferation, apoptosis, and metastasis ability, though the responsible molecular mechanism has not been well elucidated. In this study, we sought to determine the expression patterns of miR-197 targeted genes and to explore their potential functions, participating Pathways and the networks that are involved in the biological behavior of human uterine leiomyoma. After transfection of human uterine leiomyoma cells with miR-197, we confirmed the expression level of miR-197 using quantitative real-time PCR (qRT-PCR), and we detected the gene expression profiles after miR-197 over-expression through DNA microarray analysis. Further, we performed GO and Pathway analysis. The dominantly dys-regulated genes, which were up- or down-regulated by more than 10-fold, compared with parental cells, were confirmed using qRT-PCR technology. Compared with the control group, miR-197 was up-regulated by 30-fold after miR-197 lentiviral transfection. The microarray data showed that 872 genes were dys-regulated by more than 2-fold in human uterine leiomyoma cells after miR-197 overexpression, including 537 up-regulated and 335 down-regulated genes. The GO analysis indicated that the dys-regulated genes were primarily involved in response to stimuli, multicellular organ processes, and the signaling of biological progression. Further, Pathway analysis data showed that these genes participated in regulating several signaling Pathways, including the JAK/STAT signaling Pathway, the Toll-like receptor signaling Pathway, and cytokine-cytokine receptor interaction. The qRT-PCR results confirmed that 17 of the 66 selected genes, which were up- or down-regulated more than 10-fold by miR-197, were consistent with the microarray results, including tumorigenesis-related genes, such as DRT7, SLC549, SFMBT2, FLJ37956

  11. Aberrant over-expression of a forkhead family member, FOXO1A, in a brain tumor cell line

    International Nuclear Information System (INIS)

    Dallas, Peter B; Egli, Simone; Terry, Philippa A; Kees, Ursula R

    2007-01-01

    The mammalian FOXO (forkhead box, O subclass) proteins are a family of pleiotropic transcription factors involved in the regulation of a broad range of cellular processes critical for survival. Despite the essential and diverse roles of the FOXO family members in human cells and their involvement in tumor pathogenesis, the regulation of FOXO expression remains poorly understood. We have addressed the mechanisms underlying the high level of expression of the FOXO1A gene in a cell line, PER-453, derived from a primitive neuroectodermal tumor of the central nervous system (CNS-PNET). The status of the FOXO1A locus in the PER-453 CNS-PNET cell line was investigated by Southern blotting and DNA sequence analysis of the proximal promoter, 5'-UTR, open reading frame and 3'-UTR. FOXO1A expression was assessed by conventional and quantitative RT-PCR, Northern and Western blotting. Quantitative real-time RT-PCR (qRT-PCR) data indicated that after normalization to ACTB mRNA levels, canonical FOXO1A mRNA expression in the PER-453 cell line was 124-fold higher than the average level of five other CNS-PNET cell lines tested, 24-fold higher than the level in whole fetal brain, and 3.5-fold higher than the level in fetal brain germinal matrix cells. No mutations within the FOXO1A open reading frame or gross rearrangements of the FOXO1A locus were detected. However, a single nucleotide change within the proximal promoter and several nucleotide changes within the 3'-UTR were identified. In addition, two novel FOXO1A transcripts were isolated that differ from the canonical transcript by alternative splicing within the 3'-UTR. The CNS-PNET cell line, PER-453, expresses FOXO1A at very high levels relative to most normal and cancer cells from a broad range of tissues. The FOXO1A open reading frame is wild type in the PER-453 cell line and the abnormally high FOXO1A mRNA expression is not due to mutations affecting the 5'-UTR or proximal promoter. Over expression

  12. Shape memory polymer nanocomposites for application of multiple-field active disassembly: experiment and simulation.

    Science.gov (United States)

    Carrell, John; Zhang, Hong-Chao; Wang, Shiren; Tate, Derrick

    2013-11-19

    Active disassembly (AD) uses innovative materials that can perform a designed disassembly action by the application of an external field. AD provides improvements over current disassembly processes by limiting machine or manual labor and enabling batch processing for end-of-life products. With improved disassembly operations, more reuse of components and purer recycling streams may be seen. One problem with AD, however, has been with the single-field actuation because of the probability of accidental disassembly. This presentation will discuss the application of shape memory polymer (SMP) nanocomposites in a new AD process. This novel AD process requires multiple-field actuation of the SMP nanocomposite fastener. In the analysis of this AD process, thermal and magnetic field tests were performed on the SMP nanocomposite. From these tests, finite-element analysis was performed to model and simulate the multiple-field AD process. The results of the simulations provide performance variables for the AD process and show a better performance time for the SMP nanocomposite fastener than for a comparable SMP fastener.

  13. Spatio-temporal model for multiple ChIP-seq experiments

    NARCIS (Netherlands)

    Ranciati, Saverio; Viroli, Cinzia; Wit, Ernst

    2015-01-01

    The increasing availability of ChIP-seq data demands for advanced statistical tools to analyze the results of such experiments. The inherent features of high-throughput sequencing output call for a modelling framework that can account for the spatial dependency between neighboring regions of the

  14. Parental Incarceration and Multiple Risk Experiences: Effects on Family Dynamics and Children's Delinquency

    Science.gov (United States)

    Aaron, Lauren; Dallaire, Danielle H.

    2010-01-01

    Children of incarcerated parents are exposed to factors that place them at risk for delinquency. Few studies have examined the effects of having an incarcerated parent after controlling for other experiences such as contextual risk factors and family processes. Past studies have also not examined effects of recent, but not current, parental…

  15. Multiple Intimate Partner Violence Experiences: Knowledge, Access, Utilization and Barriers to Utilization of Resources by Women of the African Diaspora.

    Science.gov (United States)

    Sabri, Bushra; Huerta, Julia; Alexander, Kamila A; St Vil, Noelle M; Campbell, Jacquelyn C; Callwood, Gloria B

    2015-11-01

    This study examined knowledge, access, utilization, and barriers to use of resources among Black women exposed to multiple types of intimate partner violence in Baltimore, Maryland and the U.S. Virgin Islands (USVI). We analyzed quantitative survey data collected by 163 women recruited from primary care, prenatal or family planning clinics in Baltimore and the USVI. In addition we analyzed qualitative data from in-depth interviews with 11 women. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed using thematic analysis. A substantial proportion of Black women with multiple types of violence experiences lacked knowledge of, did not have access to, and did not use resources. Barriers to resource use were identified at the individual, relationship, and community levels. There is need for programs to develop awareness, promote access and utilization of resources, and eliminate barriers to resource use among abused Black women.

  16. Fission time-scale in experiments and in multiple initiation model

    Energy Technology Data Exchange (ETDEWEB)

    Karamian, S. A., E-mail: karamian@nrmail.jinr.ru [Joint Institute for Nuclear Research (Russian Federation)

    2011-12-15

    Rate of fission for highly-excited nuclei is affected by the viscose character of the systemmotion in deformation coordinates as was reported for very heavy nuclei with Z{sub C} > 90. The long time-scale of fission can be described in a model of 'fission by diffusion' that includes an assumption of the overdamped diabatic motion. The fission-to-spallation ratio at intermediate proton energy could be influenced by the viscosity, as well. Within a novel approach of the present work, the cross examination of the fission probability, time-scales, and pre-fission neutron multiplicities is resulted in the consistent interpretation of a whole set of the observables. Earlier, different aspects could be reproduced in partial simulations without careful coordination.

  17. POOR HEMOPOIETIC STEM CELL MOBILIZERS IN MULTIPLE MYELOMA : A SINGLE INSTITUTION EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Guillermo Jose Ruiz-Delgado

    2010-06-01

    Full Text Available In a single institution, in a group of 28 myeloma patients deemed eligible for autologous transplant, stem cell mobilization was attempted using filgrastim: 26 individuals were given 31 autografts employing 1-4 (median three apheresis sessions, to obtain a target stem cell dose of 1 x 106 CD34 viable cells / Kg of the recipient. The median number of grafted CD34 cells was 7.56 x 106  / Kg of the recipient; the range being 0.92 to 14.8.  By defining as poor mobilizers individuals in which a cell collection of 1 x 106 CD34 viable cells / Kg was better (80% at 80 months than those grafted with < 1 x 106 CD34 viable cells / Kg (67% at 76 months. Methods to improve stem cell mobilization are needed and may result in obtaining better results when autografting multiple myeloma patients.

  18. Natural history of multiple sclerosis from the Indian perspective: Experience from a tertiary care hospital.

    Science.gov (United States)

    Jena, Subhransu S; Alexander, Mathew; Aaron, Sanjith; Mathew, Vivek; Thomas, Maya Mary; Patil, Anil K; Sivadasan, Ajith; Muthusamy, Karthik; Mani, Sunithi; Rebekah, J Grace

    2015-01-01

    Multiple sclerosis (MS) has a spectrum of heterogeneity, as seen in western and eastern hemispheres, in the clinical features, topography of involvement and differences in natural history. To study the clinical spectrum, imaging, and electrophysiological as well as cerebrospinal fluid (CSF) characteristics and correlate them with outcome. Retrospective analysis of MS patients during a period of 20 years. Cases were selected according to recent McDonald's criteria (2010), They were managed in the Department of Neurology, Christian Medical College, Vellore. Chi-square and Fisher's exact tests were used for categorical variables. Multiple binary logistic regressions were done to assess significance. Kaplan-Meier curves were drawn to estimate the time to irreversible disability. A total of 157 patients with female preponderance (55%) were included. The inter quartile range duration of follow-up was 9.1 (8.2, 11) years for 114 patients, who were included for final outcome analysis. Relapsing remitting MS (RRMS) (54.1%) was the most common type of MS seen. RRMS had a significantly better outcome (odds ratio: 0.12, 95% confidence interval: 0.02-0.57, P = 0.008) compared to progressive form of MS (primary progressive, secondary progressive). The Expanded Disability Status Scale score of patients at presentation and at final follow-up was 4.4 ± 1.31 and 4.1 ± 2.31, respectively. During the first presentation, polysymptomatic manifestations like motor and sphincteric involvement, incomplete recovery from the first attack; and, during the disease course, bowel, bladder, cerebellar and pyramidal affliction, predicted a worse outcome. A high incidence of optico-spinal presentation, predominance of RRMS and a low yield on cerebrospinal fluid (CSF) studies are the major findings of our study. A notable feature was the analysis of prognostic markers of disability.

  19. An optoelectronic detecting based environment perception experiment for primer students using multiple-layer laser scanner

    Science.gov (United States)

    Wang, Shifeng; Wang, Rui; Zhang, Pengfei; Dai, Xiang; Gong, Dawei

    2017-08-01

    One of the motivations of OptoBot Lab is to train primer students into qualified engineers or researchers. The series training programs have been designed by supervisors and implemented with tutoring for students to test and practice their knowledge from textbooks. An environment perception experiment using a 32 layers laser scanner is described in this paper. The training program design and laboratory operation is introduced. The four parts of the experiments which are preparation, sensor calibration, 3D space reconstruction, and object recognition, are the participating students' main tasks for different teams. This entire program is one of the series training programs that play significant role in establishing solid research skill foundation for opto-electronic students.

  20. Multiple sclerosis patients' experiences in relation to the impact of the kinect virtual home-exercise programme: a qualitative study.

    Science.gov (United States)

    Palacios-Ceña, Domingo; Ortiz-Gutierrez, Rosa M; Buesa-Estellez, Almudena; Galán-Del-Río, Fernando; Cachon Perez, José M; Martínez-Piedrola, Rosa; Velarde-Garcia, Juan F; Cano-DE-LA-Cuerda, Roberto

    2016-06-01

    Neurorehabilitation programs are among the most popular therapies aimed at reducing the disabilities that result from multiple sclerosis. Video games have recently gained importance in the rehabilitation of patients with motor neurological dysfunctions. Currently, the studies describing the perspective of patients with multiple sclerosis who have participated in rehabilitation programmes via home-based video games are almost inexistent. The aim of this paper was to explore the experiences of multiple sclerosis patients who performed a virtual home-exercise programme using Kinect. A qualitative research enquiry was conducted as part of a study that examined postural control and balance after a 10-week Kinect home-exercise programme in adults with multiple sclerosis. Patients were recruited from a Neurology Unit of a University Hospital. The inclusion criteria were: subjects aged between 20 and 60 years, diagnosed with multiple sclerosis for over 2 years based on the McDonald Criteria; with an EDSS score ranging from 3 to 5. Purposeful sampling method was implemented. The data collection consisted of unstructured interviews, using open questions, and thematic analysis was conducted. Guidelines for conducting qualitative studies established by the Consolidated Criteria for Reporting Qualitative Research were followed. Twenty-four patients with a mean age of 36.69 were included. Four main themes emerged from the data: 1) regaining previous capacity and abilities. The patients described how, after the treatment with Kinect they felt more independent; 2) sharing the disease. The patients sharing the experience of living with MS with their family, thanks to the use of Kinect; 3) adapting to the new treatment. This refers to how the use of the videogame console incorporated novelties to their rehabilitation programme; and 4) comparing oneself. This refers to the appearance of factors that motivate the patient during KVHEP. The patients' experiences gathered in this study

  1. Perceived discrimination and psychotic experiences across multiple ethnic groups in the United States.

    Science.gov (United States)

    Oh, Hans; Yang, Lawrence H; Anglin, Deidre M; DeVylder, Jordan E

    2014-08-01

    The objective of this study was to examine the relationship between perceived discrimination and psychotic experiences (PE) using validated measures of discrimination and a racially/ethnically diverse population-level sample. Data were drawn from two population-level surveys (The National Latino and Asian American Survey and The National Survey of American Life), which were analyzed together using survey weights and stratification variables. The analytic sample (N=8990) consisted of Latino, Asian, African-American, and Afro-Caribbean adults living in the United States. Separate unadjusted and adjusted multivariable logistic regression models were used, first to examine the crude bivariate relationship between perceived discrimination and PE, and second to examine the relationship adjusting for demographic variables. Adjusted logistic regression models were also used to examine the relationships between perceived discrimination and specific sub-types of PE (auditory and visual hallucinatory experiences, and delusional ideation). When compared to individuals who did not report any discrimination, those who reported the highest levels of discrimination were significantly more likely to report both 12-month PE (Adjusted OR=4.590, pPerceived discrimination is associated with the increased probability of reporting psychotic experiences in a linear Fashion in the US general population. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Parental incarceration and multiple risk experiences: effects on family dynamics and children's delinquency.

    Science.gov (United States)

    Aaron, Lauren; Dallaire, Danielle H

    2010-12-01

    Children of incarcerated parents are exposed to factors that place them at risk for delinquency. Few studies have examined the effects of having an incarcerated parent after controlling for other experiences such as contextual risk factors and family processes. Past studies have also not examined effects of recent, but not current, parental incarceration on children. The present study examines an archival dataset, in which children aged 10-14 years and their parents/guardians reported children's risk experiences (e.g., exposure to poverty, parental substance use), family processes (e.g., level of family victimization, family conflict), and children's delinquent behaviors at two time points. Parents also reported their recent and past incarceration history. Hierarchical linear regression analyses show that a history of parental incarceration predicted family victimization, delinquent behaviors of children's older siblings, and delinquent behaviors of the child participants, over and above children's demographic characteristics and other risk experiences. Recent parental incarceration predicted family conflict, family victimization, and parent-reports of children's delinquency after also controlling for previous parental incarceration. The role of family processes in research and intervention directions involving children of incarcerated parents is discussed.

  3. The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma

    DEFF Research Database (Denmark)

    Anderton, J A; Bose, S; Vockerodt, M

    2011-01-01

    ), an Epstein-Barr virus (EBV) associated malignancy. KDM6B is over-expressed in primary HL and induced by the EBV oncogene, latent membrane protein (LMP1) in GC B cells, the presumptive progenitors of HL. Consistent with these observations, we found that KDM6B transcriptional targets in GC B cells are enriched...

  4. CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

    International Nuclear Information System (INIS)

    Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion; Gahl, Anja; Scheeder, Martin R.L.; Cardoso, M. Cristina; Leonhardt, Heinrich; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika

    2005-01-01

    To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1α (CPT1α). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1α transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1α over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1α over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1α, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo

  5. The Arabidopsis mutant iop1 exhibits induced over-expression of the plant defensin gene PDF1.2 and enhanced pathogen resistance

    NARCIS (Netherlands)

    Penninckx, I.A.M.A.; Eggermont, K.; Schenk, P.M.; Ackerveken, van den G.; Cammue, B.P.A.; Thomma, B.P.H.J.

    2003-01-01

    Jasmonate and ethylene are concomitantly involved in the induction of the Arabidopsis plant defensin gene PDF1.2. To define genes in the signal transduction pathway leading to the induction of PDF1.2, we screened for mutants with induced over-expression of a β-glucuronidase reporter, under the

  6. Chaperonin GroEL/GroES Over-Expression Promotes Aminoglycoside Resistance and Reduces Drug Susceptibilities in Escherichia coli Following Exposure to Sublethal Aminoglycoside Doses

    DEFF Research Database (Denmark)

    Goltermann, Lise; Sarusie, Menachem V; Bentin, Thomas

    2016-01-01

    Antibiotic resistance is an increasing challenge to modern healthcare. Aminoglycoside antibiotics cause translation corruption and protein misfolding and aggregation in Escherichia coli. We previously showed that chaperonin GroEL/GroES depletion and over-expression sensitize and promote short...

  7. A quality control of proteomic experiments based on multiple isotopologous internal standards

    Directory of Open Access Journals (Sweden)

    Adele Bourmaud

    2015-09-01

    Full Text Available The harmonization of proteomics experiments facilitates the exchange and comparison of results. The definition of standards and metrics ensures reliable and consistent data quality. An internal quality control procedure was developed to assess the different steps of a proteomic analysis workflow and perform a system suitability test. The method relies on a straightforward protocol using a simple mixture of exogenous proteins, and the sequential addition of two sets of isotopically labeled peptides added to reference samples. This internal quality control procedure was applied to plasma samples to demonstrate its easy implementation, which makes it generic for most proteomics applications.

  8. Cellobiohydrolase B of Aspergillus niger over-expressed in Pichia pastoris stimulates hydrolysis of oil palm empty fruit bunches

    Directory of Open Access Journals (Sweden)

    James Sy-Keen Woon

    2017-10-01

    Full Text Available Background Aspergillus niger, along with many other lignocellulolytic fungi, has been widely used as a commercial workhorse for cellulase production. A fungal cellulase system generally includes three major classes of enzymes i.e., β-glucosidases, endoglucanases and cellobiohydrolases. Cellobiohydrolases (CBH are vital to the degradation of crystalline cellulose present in lignocellulosic biomass. However, A. niger naturally secretes low levels of CBH. Hence, recombinant production of A. niger CBH is desirable to increase CBH production yield and also to allow biochemical characterisation of the recombinant CBH from A. niger. Methods In this study, the gene encoding a cellobiohydrolase B (cbhB from A. niger ATCC 10574 was cloned and expressed in the methylotrophic yeast Pichia pastoris X-33. The recombinant CBHB was purified and characterised to study its biochemical and kinetic characteristics. To evaluate the potential of CBHB in assisting biomass conversion, CBHB was supplemented into a commercial cellulase preparation (Cellic® CTec2 and was used to hydrolyse oil palm empty fruit bunch (OPEFB, one of the most abundant lignocellulosic waste from the palm oil industry. To attain maximum saccharification, enzyme loadings were optimised by response surface methodology and the optimum point was validated experimentally. Hydrolysed OPEFB samples were analysed using attenuated total reflectance FTIR spectroscopy (ATR-FTIR to screen for any compositional changes upon enzymatic treatment. Results Recombinant CBHB was over-expressed as a hyperglycosylated protein attached to N-glycans. CBHB was enzymatically active towards soluble substrates such as 4-methylumbelliferyl-β-D-cellobioside (MUC, p-nitrophenyl-cellobioside (pNPC and p-nitrophenyl-cellobiotrioside (pNPG3 but was not active towards crystalline substrates like Avicel® and Sigmacell cellulose. Characterisation of purified CBHB using MUC as the model substrate revealed that optimum

  9. MRMer, an interactive open source and cross-platform system for data extraction and visualization of multiple reaction monitoring experiments.

    Science.gov (United States)

    Martin, Daniel B; Holzman, Ted; May, Damon; Peterson, Amelia; Eastham, Ashley; Eng, Jimmy; McIntosh, Martin

    2008-11-01

    Multiple reaction monitoring (MRM) mass spectrometry identifies and quantifies specific peptides in a complex mixture with very high sensitivity and speed and thus has promise for the high throughput screening of clinical samples for candidate biomarkers. We have developed an interactive software platform, called MRMer, for managing highly complex MRM-MS experiments, including quantitative analyses using heavy/light isotopic peptide pairs. MRMer parses and extracts information from MS files encoded in the platform-independent mzXML data format. It extracts and infers precursor-product ion transition pairings, computes integrated ion intensities, and permits rapid visual curation for analyses exceeding 1000 precursor-product pairs. Results can be easily output for quantitative comparison of consecutive runs. Additionally MRMer incorporates features that permit the quantitative analysis experiments including heavy and light isotopic peptide pairs. MRMer is open source and provided under the Apache 2.0 license.

  10. Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity.

    Science.gov (United States)

    Koehler, Jürgen; Feneberg, Wolfgang; Meier, Martin; Pöllmann, Walter

    2014-09-01

    This detailed medical charts' data collection study conducted at a multiple sclerosis (MS) clinic in Germany evaluated the effectiveness of tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray in patients with resistant MS spasticity. Over a 15-month timeframe, THC:CBD spray was initiated in 166 patients. Mean follow-up was 9 months. In all, 120 patients remained on treatment for a response rate of 72%. THC:CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. Among responders, the mean spasticity 0-10 numerical rating scale (NRS) score decreased by 57%, from 7.0 before treatment to 3.0 within 10 days of starting THC:CBD spray. The mean dosage was 4 sprays/day. Most patients who withdrew from treatment (40/46) had been receiving THC:CBD spray for less than 60 days. Main reasons for treatment discontinuation were: adverse drug reactions, mainly dizziness, fatigue and oral discomfort (23 patients; 13.9%); lack of efficacy (14 patients; 8.4%); or need for a baclofen pump (9 patients; 5.4%). No new safety signals were noted with THC:CBD spray during the evaluation period. In this routine clinical practice setting at an MS clinic in Germany, THC:CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.

  11. Evolving Non-Dominated Parameter Sets for Computational Models from Multiple Experiments

    Science.gov (United States)

    Lane, Peter C. R.; Gobet, Fernand

    2013-03-01

    Creating robust, reproducible and optimal computational models is a key challenge for theorists in many sciences. Psychology and cognitive science face particular challenges as large amounts of data are collected and many models are not amenable to analytical techniques for calculating parameter sets. Particular problems are to locate the full range of acceptable model parameters for a given dataset, and to confirm the consistency of model parameters across different datasets. Resolving these problems will provide a better understanding of the behaviour of computational models, and so support the development of general and robust models. In this article, we address these problems using evolutionary algorithms to develop parameters for computational models against multiple sets of experimental data; in particular, we propose the `speciated non-dominated sorting genetic algorithm' for evolving models in several theories. We discuss the problem of developing a model of categorisation using twenty-nine sets of data and models drawn from four different theories. We find that the evolutionary algorithms generate high quality models, adapted to provide a good fit to all available data.

  12. Multiple scattering of low energy rare gas ions: a comparison of experiment and computer simulation

    International Nuclear Information System (INIS)

    Heiland, W.; Taglauer, E.; Robinson, M.T.

    1976-01-01

    Some aspects of ion scattering below a few keV have been interpreted by multiple scattering. This can partly be simulated by chain or string models, where the single crystal surface is replaced by a chain of atoms. The computer program MARLOWE allows a simulation of solid-ion interaction, which is much closer to reality, e.g. the crystal is three-dimensional, includes lattice vibrations, electronic stopping power, different scattering potentials, etc. It is shown that the energy of the reflected ions as a function of the primary energy, lattice constant, impact angle and scattering angle can be understood within the string model. These results of the string model are confirmed by the MARLOWE calculations. For an interpretation of the measured intensities the simple string model is insufficient, whereas with MARLOWE reasonable agreement with experimental data may be achieved, if the thermal vibrations of the lattice atoms are taken into account. The experimental data include Ne + →Ni, Ne + →Ag and preliminary data on Ne + →W. The screening parameters of the scattering potentials are estimated for these ion-atom combinations. The results allow some conclusions about surface Debye temperatures. (Auth.)

  13. Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: The Mayo Clinic experience

    International Nuclear Information System (INIS)

    Miller, Robert C.; Lachance, Daniel H.; Lucchinetti, Claudia F.; Keegan, B. Mark; Gavrilova, Ralitza H.; Brown, Paul D.; Weinshenker, Brian G.; Rodriguez, Moses

    2006-01-01

    Purpose: The aim of this study was a retrospective assessment of neurotoxicity in patients with multiple sclerosis (MS) receiving external beam radiotherapy (EBRT) to the brain. Methods and Materials: We studied 15 consecutively treated patients with MS who received brain EBRT. Neurologic toxicity was assessed with the Common Toxicity Criteria v.3.0. Results: Median follow-up for the 5 living patients was 6.0 years (range, 3.3-27.4 years). No exacerbation of MS occurred in any patient during EBRT. Five patients had Grade 4 neurologic toxicity and 1 had possible Grade 5 toxicity. Kaplan-Meier estimated risk of neurotoxicity greater than Grade 4 at 5 years was 57% (95% confidence interval, 27%-82%). Toxicity occurred at 37.5 to 54.0 Gy at a median of 1.0 year (range, 0.2-4.3 years) after EBRT. Univariate analysis showed an association between opposed-field irradiation of the temporal lobes, central white matter, and brainstem and increased risk of neurotoxicity (p < 0.04). Three of 6 cases of toxicity occurred in patients treated before 1986. Conclusions: External beam radiotherapy of the brain in patients with MS may be associated with an increased risk of neurotoxicity compared with patients without demyelinating illnesses. However, this risk is associated with treatment techniques that may not be comparable to modern, conformal radiotherapy

  14. Multiple genetic interaction experiments provide complementary information useful for gene function prediction.

    Directory of Open Access Journals (Sweden)

    Magali Michaut

    Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.

  15. Mitoxantrone in the treatment of multiple sclerosis: a single-center experience

    Directory of Open Access Journals (Sweden)

    Özlem Taşkapılıoğlu

    2012-06-01

    Full Text Available OBJECTIVE: To investigate the secondary progressive multiple sclerosis (SPMS patients treated with mitoxantrone (MIT and discuss the effectiveness and side effects of MIT. METHODS: We retrospectively investigated 48 SPMS patients who completed or were still receiving MIT treatment. Expanded Disability Status Scale (EDSS scores of the patients were determined who had detailed examination before the treatment. Complete blood count, urine examination, chest x-ray, kidney and liver function tests, transthoracic echocardiography were performed at initiation and during follow-up and 10 mg/m2 MIT was administered every three months. The data were assessed in order to determine the effectiveness and side effects. RESULTS: A total of 48 patients, 34 women and 14 men, had an age of 42 (26-55 years at the initiation of MIT treatment. The duration of the treatment was 12 (3-30 months. The median EDSS scores were 6 (4-8 before the treatment and 6 (4-9 after the treatment. EDSS scores improved in 6 patients, deteriorated in 12 patients and 30 patients remained with stable EDSS scores during the treatment. Seventeen patients had no side effects however 31 patients developed side effects. CONCLUSION: On the basis of this study, which is a clinical assessment of the effectiveness and side effects of MIT, we conclude that MIT can limit disability in SPMS patients and it is useful in treating SPMS patients due to favorable risk-benefit ratio

  16. The multicenter experience with bendamustine in the treatment of relapsed and refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    S. V. Voloshin

    2015-01-01

    Full Text Available Relapsed and refractory (R/R multiple myeloma (MM constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short. In patients with R/R MM after therapy of bortezomib and/or immunomodulators a bendamustine-based treatment can be used as “salvage”.In this retrospective analysis we have identified 32 patients with R/R MM by means of case research, have been bendamustine-based treated at Hematological Clinics of Russian Federation since 2011. Median age was 67 (43–81 years, the female/male ratio was 2.5:1. After in median 2 (1–7 lines of prior therapy patients received in median 3 (1–9 cycles of bendamustine-based therapy. Bendamustine dosage was 70–120 mg/m2 /day on 2 days of each 28-day cycle until progressive disease or intolerability. Overall rate response was 56.2 %: 21.9 % partial response, stable disease 34.4 %. Median time to progression was 5.3 (0.8–18.0 months and median overall survival was 25.4 (0.8–47.1 months. Hematologic toxicity was in 53.2 % of patients.

  17. Studies on laser beam propagation and stimulated scattering in multiple beam experiments

    International Nuclear Information System (INIS)

    Labaune, C.; Lewis, K.; Bandulet, H.; Lewis, K.; Depierreux, S.; Huller, S.; Masson-Laborde, P.E.; Pesme, D.; Riazuelo, G.

    2006-01-01

    The propagation and stimulated scattering of intense laser beams interacting with underdense plasmas are two important issues for inertial confinement fusion (ICF). The purpose of this work was to perform experiments under well-controlled interaction conditions and confront them with numerical simulations to test the physics included in the codes. Experimental diagnostics include time and space resolved images of incident and SBS light and of SBS-ion acoustic activity. New numerical diagnostics, including similar constraints as the experimental ones and the treatment of the propagation of the light between the emitting area and the detectors, have been developed. Particular care was put to include realistic plasma density and velocity profiles, as well as laser pulse shape in the simulations. In the experiments presented in this paper, the interaction beam was used with a random phase plate (RPP) to produce a statistical distribution of speckles in the focal volume. Stimulated Brillouin Scattering (SBS) was described using a decomposition of the spatial scales which provides a predictive modeling of SBS in an expanding mm-scale plasma. Spatial and temporal behavior of the SBS-ion acoustic waves was found to be in good agreement with the experimental ones for two laser intensities. (authors)

  18. Air MEDEVAC in case of multiple casualties – The experience of civilian-military cooperation in RoAF

    Directory of Open Access Journals (Sweden)

    Dragoș C. Tudose

    2016-07-01

    Full Text Available Introduction: Starting September 2010 in Romania was created the Military Emergency Medical Service (SMMU by the Ministry of National Defense, which has as main mission to provide first aid and save the lives of military personnel during military operations using special equipped MEDEAVC aircraft. Nationwide exist the national emergency system which operates thru 112- SMURD acting in support of the civilian population. In case of accidents with multiple victims the experience has shown the need for collaboration between the two systems, in order to save lives. In the last 5 years there has been an increasing Airlift missions (MEDEVAC with multiple victims executed by joint civil-military medical teams using military aircraft. Material and methods. This paper provides a review of the most important aspects of particularities, advantages and disadvantages of this type of medical transport using the MEDEVAC missions based study carried out by the Air Force in recent years. Results and conclusions. Performing these tasks presents challenges to mission planning, use of medical equipment and procedures, command-control system, exercise programs jointly joint medical teams and, of course, managing a large number of patients in flight. The large number of patients transported safely and in the shortest time, regardless of weather conditions recommends this type of medical intervention. Given the Romanian military presence in various theaters and that NATO strategic medical evacuation is a national responsibility, the capacity of air transport in case multiple casualties is a priority.

  19. THE EXPERIENCE OF TREATMENT OF MULTIPLE BASALIOMA IN GORLIN-GOLTZ SYNDROME

    Directory of Open Access Journals (Sweden)

    E. I. Tret'yakova

    2016-01-01

    Full Text Available Aim: To assess clinical efficacy of the treatment options for multiple basalioma in patients with Gorlin-Goltz syndrome. Materials and methods: We retrospectively analyzed the results of various treatments in 23  patients with the Gorlin-Goltz syndrome for the time period of 25  years. Four treatment groups were formed depending on the treatment method. In the group 1, 18 patients were cryodestructed, with elimination of 158  superficial and ulcer basaliomas T₁N₀M₀, T₂N₀M₀, T₃N₀M₀. In the group 2, 5  patients received photodynamic therapy, with removal of 78 superficial, nodular and ulcer basaliomas T₁N₀M₀, T₂N₀M₀, T₃N₀M₀. In the group 3, 3  patients were administered laser-induced thermic therapy with removal of 16  superficial basaliomas T₁N₀M₀. In the group 4, 5 patients received topical chemotherapy with Mardil Selen, with removal of 18  superficial and ulcer basaliomas T₁N₀M₀. As radiation sources for photodynamic and laser-induced thermic therapy we used laser equipment with copper vaporization and adjusted wave length Metalaz 1  and semiconductor infrared laser LAMI. The photodynamic therapy was administered with photosensitizers Photohem and Radachlorin. The results of treatment and relapse-free periods were assessed annually in all patients up to 5  years after treatment. Results: After cryodestruction, 83.3%  of patients with Gorlin-Goltz syndrome were cured (153  basaliomas and additional 16.7%  improved. Relapses during the time period from one to three years were observed in 16.7% of patients. Nine (9 basaliomas relapsed. After photodynamic therapy, 80%  of patients (73  basaliomas were cured and 20%  improved. Relapses from 1  to 3  years were observed in 20% of patients (2 basaliomas. After laser-induced thermic therapy 100%  of patients (16  basaliomas were cured, and relapses from 1  to 2  years were registered in 33%  of patients (4 basaliomas. After

  20. EXPERIENCE OF SUCCESSFUL ACNEFORM ERUPTIONS TREATMENT IN PATIENT WITH MULTIPLE MELANOMA

    Directory of Open Access Journals (Sweden)

    O. V. Minkina

    2016-01-01

    Full Text Available Objective: to describe the results of the joint monitoring and diversified treatment of oncologists and dermatologists those patient with multiple recurrent melanoma who received over a long period a targeted anti-cancer therapy, which was complicated by side-effect as widespread acneform rush, resistant to traditional treatment. Patient A., born in 1988, was followed up and got a treatment more than 2 years in oncology out-patient clinic diagnosed with “Melanoma of the front surface of the left leg T2bN0M0 IIA”. Subsequently, the patient was verified metastasis in the inginal lymph nodes, in the soft tissues of the hips, to liver. Acute adverse reaction has developed in a short time after getting the anti-tumor target therapy as generalized acneform rush and itching of the skin. Skin symptoms accompanied by pronounced psychological and emotional stress, therefore, dermatologists have been invited to provide additional medical assistance to this patient. Due to the fact that subsequent traditional anti-acne algorithms of topical and oral treatment was not such effective, there was made a decision to use an alternative supporting external therapy, which did not have similar examples of usage previously. Results. External application of tacrolimus ointment in combination with other drugs and then as a mono-therapy, allows us in a rather short period achieve a stable and pronounced regression of skin pathological lesions, to return to the previously cancelled initial drug dose of the anti-tumor target therapy, to change significantly components of the patient’s quality of life. Conclusion. The search for additional and alternative treatment approaches for similar patients, as in our case, remains relevant for specialists and patients themselves. This case is an example of alternative approach to the tacrolimus topical application in patient with drug-mediated acneform rush.

  1. Rural electrification with multiple actors - the experience of the brazilian state of Sao Paulo

    International Nuclear Information System (INIS)

    Pazzini, Luiz Henrique Alves; Pelegrini, Marcelo Aparecido; Ribeiro, Fernando Selles; Galvao, Luiz Claudio Ribeiro

    1999-01-01

    The lack of resources and the new scenery of private utilities turn necessary to look for the ways that allow to illuminate the rural zone. Several international papers show the involvement of different segments of the society as being a viable alternative to execute this goal. This paper analyses the experience of Sao Paulo in the practice of a program of rural electrification in which the society is involved. The model, the operational difficulties and the alternatives made to agile program are appraised. The main conclusion is that, in spite of the difficulties, the model in which the society is included is a viable alternative to solve the subject of the lack of energy in the countryside. (author)

  2. Flocking multiple microparticles with automatically controlled optical tweezers: solutions and experiments.

    Science.gov (United States)

    Chen, Haoyao; Wang, Can; Lou, Yunjiang

    2013-06-01

    This paper presents an efficient approach to achieve microparticles flocking with robotics and optical tweezers technologies. All particles trapped by optical tweezers can be automatically moved toward a predefined region without collision. The main contribution of this paper lies in the proposal of several solutions to the flocking manipulation of microparticles in microenvironments. First, a simple flocking controller is proposed to generate the desired positions and velocities for particles' movement. Second, a velocity saturation method is implemented to prevent the desired velocities from exceeding a safe limit. Third, a two-layer control architecture is proposed for the motion control of optical tweezers. This architecture can help make many robotic manipulations achievable under microenvironments. The proposed approach with these solutions can be applied to many bioapplications especially in cell engineering and biomedicine. Experiments on yeast cells with a robot-tweezers system are finally performed to verify the effectiveness of the proposed approach.

  3. Mixed-time parallel evolution in multiple quantum NMR experiments: sensitivity and resolution enhancement in heteronuclear NMR

    International Nuclear Information System (INIS)

    Ying Jinfa; Chill, Jordan H.; Louis, John M.; Bax, Ad

    2007-01-01

    A new strategy is demonstrated that simultaneously enhances sensitivity and resolution in three- or higher-dimensional heteronuclear multiple quantum NMR experiments. The approach, referred to as mixed-time parallel evolution (MT-PARE), utilizes evolution of chemical shifts of the spins participating in the multiple quantum coherence in parallel, thereby reducing signal losses relative to sequential evolution. The signal in a given PARE dimension, t 1 , is of a non-decaying constant-time nature for a duration that depends on the length of t 2 , and vice versa, prior to the onset of conventional exponential decay. Line shape simulations for the 1 H- 15 N PARE indicate that this strategy significantly enhances both sensitivity and resolution in the indirect 1 H dimension, and that the unusual signal decay profile results in acceptable line shapes. Incorporation of the MT-PARE approach into a 3D HMQC-NOESY experiment for measurement of H N -H N NOEs in KcsA in SDS micelles at 50 o C was found to increase the experimental sensitivity by a factor of 1.7±0.3 with a concomitant resolution increase in the indirectly detected 1 H dimension. The method is also demonstrated for a situation in which homonuclear 13 C- 13 C decoupling is required while measuring weak H3'-2'OH NOEs in an RNA oligomer

  4. The Experience of Persons With Multiple Sclerosis Using MS INFoRm: An Interactive Fatigue Management Resource.

    Science.gov (United States)

    Pétrin, Julie; Akbar, Nadine; Turpin, Karen; Smyth, Penelope; Finlayson, Marcia

    2018-04-01

    We aimed to understand participants' experiences with a self-guided fatigue management resource, Multiple Sclerosis: An Interactive Fatigue Management Resource ( MS INFoRm), and the extent to which they found its contents relevant and useful to their daily lives. We recruited 35 persons with MS experiencing mild to moderate fatigue, provided them with MS INFoRm, and then conducted semistructured interviews 3 weeks and 3 months after they received the resource. Interpretive description guided the analysis process. Findings indicate that participants' experience of using MS INFoRm could be understood as a process of change, influenced by their initial reactions to the resource. They reported experiencing a shift in knowledge, expectations, and behaviors with respect to fatigue self-management. These shifts led to multiple positive outcomes, including increased levels of self-confidence and improved quality of life. These findings suggest that MS INFoRm may have a place in the continuum of fatigue management interventions for people with MS.

  5. 13C-detected NMR experiments for automatic resonance assignment of IDPs and multiple-fixing SMFT processing

    International Nuclear Information System (INIS)

    Dziekański, Paweł; Grudziąż, Katarzyna; Jarvoll, Patrik; Koźmiński, Wiktor; Zawadzka-Kazimierczuk, Anna

    2015-01-01

    Intrinsically disordered proteins (IDPs) have recently attracted much interest, due to their role in many biological processes, including signaling and regulation mechanisms. High-dimensional 13 C direct-detected NMR experiments have proven exceptionally useful in case of IDPs, providing spectra with superior peak dispersion. Here, two such novel experiments recorded with non-uniform sampling are introduced, these are 5D HabCabCO(CA)NCO and 5D HNCO(CA)NCO. Together with the 4D (HACA)CON(CA)NCO, an extension of the previously published 3D experiments (Pantoja-Uceda and Santoro in J Biomol NMR 59:43–50, 2014. doi: 10.1007/s10858-014-9827-1 10.1007/s10858-014-9827-1 ), they form a set allowing for complete and reliable resonance assignment of difficult IDPs. The processing is performed with sparse multidimensional Fourier transform based on the concept of restricting (fixing) some of spectral dimensions to a priori known resonance frequencies. In our study, a multiple-fixing method was developed, that allows easy access to spectral data. The experiments were tested on a resolution-demanding alpha-synuclein sample. Due to superior peak dispersion in high-dimensional spectrum and availability of the sequential connectivities between four consecutive residues, the overwhelming majority of resonances could be assigned automatically using the TSAR program

  6. User participation is a family matter: A multiple case study of the experiences of older, hospitalised people and their relatives.

    Science.gov (United States)

    Nyborg, Ingrid; Danbolt, Lars J; Kirkevold, Marit

    2017-12-01

    The purpose of this multiple case study was to compare and contrast older people's and their relatives' experiences of participation in decision-making processes regarding the planning of everyday life after discharge from hospital. Internationally, patient involvement in health services is established to benefit patient health and to improve quality of the services. The literature shows that at hospital discharge, older people would benefit from better communication and more active participation of relatives in the discharge planning. Little research has been carried out on the experiences of patients and relatives as a family in this context, and even less has investigated their participation. This study used a qualitative design with a comparative multicase approach. Participants were recruited from two hospitals in Norway using a purposive sampling strategy. Semi-structured interviews were conducted with five patients and with six of their relatives. Three patterns of experiences were identified: contradicting experiences; consistent experiences of nonpreferred participation; similar, but separate experiences of user participation. User participation in the planning of everyday life following discharge appeared to be random and limited for both patients and their relatives, and conflicting for the families as a whole. The decision-making processes seemed to be limited to the hospital context and did not include the broader context of everyday life following discharge. The results underscore the importance of taking a family perspective when caring for older people. Family meetings might be a useful tool to ensure systematic assessment and integration of the perspectives of both older people and their family in the planning of follow-up care. © 2017 The Authors. Journal of Clinical Nursing Published by John Wiley & Sons Ltd.

  7. Experience of Glatiramer Acetate in the Treatment of Relapsing-Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Özlem Taşkapılıoğlu

    2012-03-01

    Full Text Available OBJECTIVE: Glatiramer acetate (GA has been shown to reduce the number of relapses and improve outcomes in relapsing-remitting multiple sclerosis (RRMS patients. The aim of this study is to investigate the efficacy and side effects of GA in RRMS patients treated with it. METHODS: We retrospectively reviewed all the records of RRMS patients treated with GA in our hospital from January 1990 to December 2010. We evaluated 114 records but 71 patients (48 women, 23 men were included in the study due to incompleteness in the other records. Demographic characteristics, time from first symptom to diagnosis, time from diagnosis to treatment, number of relapses and Expanded Disability Status Scale (EDSS scores before and after the treatment, treatment duration, side effects, the other agents used in MS treatment during the disease duration and the presence of oligoclonal bands were recorded. RESULTS: The mean age of the patients and mean GA treatment duration were 41,85±9,05 years and 28,73 months, respectively. The mean number of relapses before and after the treatment were 2.30±1.16 and 0,52±1.24 respectively. The number of relapses reduced in 64 (90,14%, unchanged in 4 (5,63% and increased in 3 (4,23% patients after GA treatment. The mean EDSS scores before and after the treatment were 2,56±1,46 and 2,04±1,68 respectively. Before GA treatment, 63,4% of all patients had EDSS scores three or more. After the treatment 50,6% of all patients had EDSS scores three or more. GA was the first choice immunomodulatory treatment in 71,8% and the second choice in 28,2% of the patients. The treatment discontinued in 8 (11,3% patients and the reason was the severe side effect in only one patient (1,4%. CONCLUSION: Glatiramer acetate decreased the number of relapses and EDSS score with tolerable side effects.

  8. [Moroccan experience in the surgical treatment of multiple hydatid cysts in the liver].

    Science.gov (United States)

    Daali, M; Hssaida, R; Zoubir, M; Borki, K

    2001-01-01

    We studied 94 cases of multiple hydatid cysts in the liver, over a period of ten years. These cases accounted for 31.3% of all cases of hydatid cysts treated surgically in the Visceral Surgery Department of Avicenne Military Hospital in Marrakech. In these patients, who were often young and male, the principal symptoms were pain in the right hypochondrium (71.3%) and hepatomegaly (24.5%). In about 10% of cases, the cysts were discovered by chance. Ultrasound and CT scans facilitated diagnosis and determination of the position of the cysts, with reliability reaching 100% for CT scans. The cysts had burst in the bile ducts in 26.6% of cases and were infected in 8 cases. They were multivesicular in 77.5% of cases. Association with hydatidosis at another site was observed in 28 cases: in the peritoneum in 15, the thorax in 7, the diaphragm in 4, the spleen in 2 and the kidney in 1 case. Surgically, the route most frequently used was double incision below the rib cage (49.5%). It is not possible to recommend one particular way to treat cysts and the most appropriate approach to treatment depends on the site, type and number of cysts. Resection of the prominent dome is the technique most frequently used (57.25%). However, in recent years, the use of cystectomy has been increasing (20.2%) due to the considerable decreases in post-operative morbidity and duration of hospital stay that it affords. The principal post-operative complications observed were abscesses under the diaphragm (6 cases), biliary leakage (5 cases), pleurisy (6 cases) and the formation of abscesses in the vestigial cavity (4 cases). The rate of morbidity in the RDS appeared high, accounting for 75% of total morbidity. Only one patient died. This patient died from severe hepatic insufficiency due to the near destruction of the liver by the hydatosis. We observed two recurrences during follow up. Both underwent further surgery and neither suffered complications.

  9. Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4+CD25+ regulatory T cells

    International Nuclear Information System (INIS)

    Jin, Yulan; Purohit, Sharad; Chen, Xueqin; Yi, Bing; She, Jin-Xiong

    2012-01-01

    Highlights: ► This is the first study to provide direct evidence of the role of Stat5b in NOD mice. ► Over-expression of wild type Stat5b transgene protects NOD mice against diabetes. ► This protection may be mediated by the up-regulation of CD4 + CD25 + Tregs. -- Abstract: The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4 + T cells and especially CD8 + T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4 + and CD8 + T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4 + CD25 + regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4 + CD25 + regulatory T cells.

  10. Track measurement in the high multiplicity environment at the CBM Experiment

    International Nuclear Information System (INIS)

    Ghosh, Pradeep

    2014-01-01

    In the Compressed Baryonic Matter (CBM) Experiment at FAIR, the Silicon Tracking System (STS) will perform track reconstruction and momentum determination of the charged particles created in interactions of heavy-ion beams with nuclear targets. The STS will consist of 8 tracking layers located at distances between 30 cm and 100 cm downstream of the target inside the 1 Tm magnetic dipole field. An ultra-low material budget is required to achieve momentum resolution of the order of Δp/p = 1%. Therefore, the front-end electronics is placed outside the physics aperture. The active volume of the STS is built from 300 μm thick double-sided silicon microstrip sensors mounted onto lightweight carbon fiber support ladders. The sensors will be read out through ultra-thin micro-cables with fast self-triggering electronics at the periphery of the stations where also other infrastructure such as cooling can be placed. In this paper, the development status of the detector system, highlighting the overview of the STS layout, tracking algorithm and performance simulations are presented.

  11. A methodology for the design of experiments in computational intelligence with multiple regression models.

    Science.gov (United States)

    Fernandez-Lozano, Carlos; Gestal, Marcos; Munteanu, Cristian R; Dorado, Julian; Pazos, Alejandro

    2016-01-01

    The design of experiments and the validation of the results achieved with them are vital in any research study. This paper focuses on the use of different Machine Learning approaches for regression tasks in the field of Computational Intelligence and especially on a correct comparison between the different results provided for different methods, as those techniques are complex systems that require further study to be fully understood. A methodology commonly accepted in Computational intelligence is implemented in an R package called RRegrs. This package includes ten simple and complex regression models to carry out predictive modeling using Machine Learning and well-known regression algorithms. The framework for experimental design presented herein is evaluated and validated against RRegrs. Our results are different for three out of five state-of-the-art simple datasets and it can be stated that the selection of the best model according to our proposal is statistically significant and relevant. It is of relevance to use a statistical approach to indicate whether the differences are statistically significant using this kind of algorithms. Furthermore, our results with three real complex datasets report different best models than with the previously published methodology. Our final goal is to provide a complete methodology for the use of different steps in order to compare the results obtained in Computational Intelligence problems, as well as from other fields, such as for bioinformatics, cheminformatics, etc., given that our proposal is open and modifiable.

  12. A methodology for the design of experiments in computational intelligence with multiple regression models

    Directory of Open Access Journals (Sweden)

    Carlos Fernandez-Lozano

    2016-12-01

    Full Text Available The design of experiments and the validation of the results achieved with them are vital in any research study. This paper focuses on the use of different Machine Learning approaches for regression tasks in the field of Computational Intelligence and especially on a correct comparison between the different results provided for different methods, as those techniques are complex systems that require further study to be fully understood. A methodology commonly accepted in Computational intelligence is implemented in an R package called RRegrs. This package includes ten simple and complex regression models to carry out predictive modeling using Machine Learning and well-known regression algorithms. The framework for experimental design presented herein is evaluated and validated against RRegrs. Our results are different for three out of five state-of-the-art simple datasets and it can be stated that the selection of the best model according to our proposal is statistically significant and relevant. It is of relevance to use a statistical approach to indicate whether the differences are statistically significant using this kind of algorithms. Furthermore, our results with three real complex datasets report different best models than with the previously published methodology. Our final goal is to provide a complete methodology for the use of different steps in order to compare the results obtained in Computational Intelligence problems, as well as from other fields, such as for bioinformatics, cheminformatics, etc., given that our proposal is open and modifiable.

  13. Disentangling multiple drivers of pollination in a landscape-scale experiment.

    Science.gov (United States)

    Schüepp, Christof; Herzog, Felix; Entling, Martin H

    2014-01-07

    Animal pollination is essential for the reproductive success of many wild and crop plants. Loss and isolation of (semi-)natural habitats in agricultural landscapes can cause declines of plants and pollinators and endanger pollination services. We investigated the independent effects of these drivers on pollination of young cherry trees in a landscape-scale experiment. We included (i) isolation of study trees from other cherry trees (up to 350 m), (ii) the amount of cherry trees in the landscape, (iii) the isolation from other woody habitats (up to 200 m) and (iv) the amount of woody habitats providing nesting and floral resources for pollinators. At the local scale, we considered effects of (v) cherry flower density and (vi) heterospecific flower density. Pollinators visited flowers more often in landscapes with high amount of woody habitat and at sites with lower isolation from the next cherry tree. Fruit set was reduced by isolation from the next cherry tree and by a high local density of heterospecific flowers but did not directly depend on pollinator visitation. These results reveal the importance of considering the plant's need for conspecific pollen and its pollen competition with co-flowering species rather than focusing only on pollinators' habitat requirements and flower visitation. It proved to be important to disentangle habitat isolation from habitat loss, local from landscape-scale effects, and direct effects of pollen availability on fruit set from indirect effects via pollinator visitation to understand the delivery of an agriculturally important ecosystem service.

  14. Integration and Testing Challenges of Small, Multiple Satellite Missions: Experiences from the Space Technology 5 Project

    Science.gov (United States)

    Sauerwein, Timothy A.; Gostomski, Thomas

    2008-01-01

    The ST5 technology demonstration mission led by GSFC of NASA's New Millennium Program managed by JPL consisted of three micro satellites (approximately 30 kg each) deployed into orbit from the Pegasus XL launch vehicle. In order to meet the launch date schedule of ST5, a different approach was required rather than the standard I&T approach used for single, room-sized satellites. The three spacecraft were designed, integrated, and tested at NASA Goddard Space Flight Center. It was determined that there was insufficient time in the schedule to perform three spacecraft I&T activities in series using standard approaches. The solution was for spacecraft #1 to undergo integration and test first, followed by spacecraft #2 and #3 simultaneously. This simultaneous integration was successful for several reasons. Each spacecraft had a Lead Test Conductor who planned and coordinated their spacecraft through its integration and test activities. One team of engineers and technicians executed the integration of all three spacecraft, learning and gaining knowledge and efficiency as spacecraft #1 integration and testing progressed. They became acutely familiar with the hardware, operation and processes for I&T, thus had the experience and knowledge to safely execute I&T for spacecraft #2 and #3. The integration team was extremely versatile; each member could perform many different activities or work any spacecraft, when needed. ST5 was successfully integrated, tested and shipped to the launch site per the I&T schedule that was planned three years previously. The I&T campaign was completed with ST5's successful launch on March 22, 2006.

  15. Design Studies for a Multiple Application Thermal Reactor for Irradiation Experiments (MATRIX)

    Energy Technology Data Exchange (ETDEWEB)

    Pope, Michael A.; Gougar, Hans D.; Ryskamp, J. M.

    2015-03-01

    The Advanced Test Reactor (ATR) is a high power density test reactor specializing in fuel and materials irradiation. For more than 45 years, the ATR has provided irradiations of materials and fuels testing along with radioisotope production. Should unforeseen circumstances lead to the decommissioning of ATR, the U.S. Government would be left without a large-scale materials irradiation capability to meet the needs of its nuclear energy and naval reactor missions. In anticipation of this possibility, work was performed under the Laboratory Directed Research and Development (LDRD) program to investigate test reactor concepts that could satisfy the current missions of the ATR along with an expanded set of secondary missions. A survey was conducted in order to catalogue the anticipated needs of potential customers. Then, concepts were evaluated to fill the role for this reactor, dubbed the Multi-Application Thermal Reactor Irradiation eXperiments (MATRIX). The baseline MATRIX design is expected to be capable of longer cycle lengths than ATR given a particular batch scheme. The volume of test space in In-Pile-Tubes (IPTs) is larger in MATRIX than in ATR with comparable magnitude of neutron flux. Furthermore, MATRIX has more locations of greater volume having high fast neutron flux than ATR. From the analyses performed in this work, it appears that the lead MATRIX design can be designed to meet the anticipated needs of the ATR replacement reactor. However, this design is quite immature, and therefore any requirements currently met must be re-evaluated as the design is developed further.

  16. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  17. Over-expression in Escherichia coli, purification and reconstitution in liposomes of the third member of the OCTN sub-family: The mouse carnitine transporter OCTN3

    Energy Technology Data Exchange (ETDEWEB)

    Scalise, Mariafrancesca; Galluccio, Michele; Pochini, Lorena [Department of Cell Biology, University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (Italy); Indiveri, Cesare, E-mail: indiveri@unical.it [Department of Cell Biology, University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (Italy)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer mOCTN3 transport protein has been cloned in pET-21a(+) and over-expressed in Escherichia coli. Black-Right-Pointing-Pointer The expressed mOCTN3 has been purified to homogeneity by Ni-chelating chromatography. Black-Right-Pointing-Pointer The protein solubilised in Triton X-100 has been reconstituted in liposomes. Black-Right-Pointing-Pointer Recombinant mOCTN3 catalyses transport of carnitine by a uniport mode. -- Abstract: pET-21a(+)-mOCTN3-6His was constructed and used for over-expression in Escherichia coli Rosetta(DE3)pLysS. After IPTG induction a protein with apparent molecular mass of 53 kDa was collected in the insoluble fraction of the cell lysate and purified by Ni{sup 2+}-chelating chromatography with a yield of 2 mg/l of cell culture. The over-expressed protein was identified with mOCTN3 by anti-His antibody and reconstitution in liposomes. mOCTN3 required peculiar conditions for optimal expression and reconstitution in liposomes. The protein catalyzed a time dependent [{sup 3}H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The K{sub m} for carnitine was 36 {mu}M. [{sup 3}H]carnitine transport was inhibited by carnitine analogues and some Cys and NH{sub 2} reagents. This paper represents the first outcome in over-expressing, in active form, the third member of the OCTN sub-family, mOCTN3, in E. coli.

  18. Over-expression in Escherichia coli, purification and reconstitution in liposomes of the third member of the OCTN sub-family: The mouse carnitine transporter OCTN3

    International Nuclear Information System (INIS)

    Scalise, Mariafrancesca; Galluccio, Michele; Pochini, Lorena; Indiveri, Cesare

    2012-01-01

    Highlights: ► mOCTN3 transport protein has been cloned in pET-21a(+) and over-expressed in Escherichia coli. ► The expressed mOCTN3 has been purified to homogeneity by Ni-chelating chromatography. ► The protein solubilised in Triton X-100 has been reconstituted in liposomes. ► Recombinant mOCTN3 catalyses transport of carnitine by a uniport mode. -- Abstract: pET-21a(+)-mOCTN3-6His was constructed and used for over-expression in Escherichia coli Rosetta(DE3)pLysS. After IPTG induction a protein with apparent molecular mass of 53 kDa was collected in the insoluble fraction of the cell lysate and purified by Ni 2+ -chelating chromatography with a yield of 2 mg/l of cell culture. The over-expressed protein was identified with mOCTN3 by anti-His antibody and reconstitution in liposomes. mOCTN3 required peculiar conditions for optimal expression and reconstitution in liposomes. The protein catalyzed a time dependent [ 3 H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The K m for carnitine was 36 μM. [ 3 H]carnitine transport was inhibited by carnitine analogues and some Cys and NH 2 reagents. This paper represents the first outcome in over-expressing, in active form, the third member of the OCTN sub-family, mOCTN3, in E. coli.

  19. Sirtuin1 Over-Expression Does Not Impact Retinal Vascular and Neuronal Degeneration in a Mouse Model of Oxygen-Induced Retinopathy

    Science.gov (United States)

    Michan, Shaday; Juan, Aimee M.; Hurst, Christian G.; Cui, Zhenghao; Evans, Lucy P.; Hatton, Colman J.; Pei, Dorothy T.; Ju, Meihua; Sinclair, David A.; Smith, Lois E. H.; Chen, Jing

    2014-01-01

    Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy. PMID:24416337

  20. XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis.

    Science.gov (United States)

    Hussain, Azhar R; Siraj, Abdul Khalid; Ahmed, Maqbool; Bu, Rong; Pratheeshkumar, Poyil; Alrashed, Alanood M; Qadri, Zeeshan; Ajarim, Dahish; Al-Dayel, Fouad; Beg, Shaham; Al-Kuraya, Khawla S

    2017-09-11

    Breast cancer is the most common cancer in females and is ranked second in cancer-related deaths all over the world in women. Despite improvement in diagnosis, the survival rate of this disease has still not improved. X-linked Inhibitor of Apoptosis (XIAP) has been shown to be over-expressed in various cancers leading to poor overall survival. However, the role of XIAP in breast cancer from Middle Eastern region has not been fully explored. We examined the expression of XIAP in more than 1000 Middle Eastern breast cancer cases by immunohistochemistry. Apoptosis was measured by flow cytometry. Protein expression was determined by western blotting. Finally, in vivo studies were performed on nude mice following xenografting and treatment with inhibitors. XIAP was found to be over-expressed in 29.5% of cases and directly associated with clinical parameters such as tumor size, extra nodal extension, triple negative breast cancer and poorly differentiated breast cancer subtype. In addition, XIAP over-expression was also significantly associated with PI3-kinase pathway protein; p-AKT, proliferative marker; Ki-67 and anti-apoptotic marker; PARP. XIAP over-expression in our cohort of breast cancer was an independent poor prognostic marker in multivariate analysis. Next, we investigated inhibition of XIAP using a specific inhibitor; embelin and found that embelin treatment led to inhibition of cell viability and induction of apoptosis in breast cancer cells. Finally, breast cancer cells treated with combination of embelin and PI3-kinase inhibitor; LY294002 synergistically induced apoptosis and caused tumor growth regression in vivo. These data suggest that XIAP may be playing an important role in the pathogenesis of breast cancer and can be therapeutically targeted either alone or in combination with PI3-kinase inhibition to induce efficient apoptosis in breast cancer cells.

  1. Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy.

    Science.gov (United States)

    Michan, Shaday; Juan, Aimee M; Hurst, Christian G; Cui, Zhenghao; Evans, Lucy P; Hatton, Colman J; Pei, Dorothy T; Ju, Meihua; Sinclair, David A; Smith, Lois E H; Chen, Jing

    2014-01-01

    Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy.

  2. Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

    OpenAIRE

    Lewis, Jo E.; Brameld, John M.; Hill, Phil; Cocco, Cristina; Noli, Barbara; Ferri, Gian-Luca; Barrett, Perry; Ebling, Francis J.P.; Jethwa, P.H.

    2017-01-01

    VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological...

  3. Enhancement of Chlorogenic Acid Production in Hairy Roots of Platycodon grandiflorum by Over-Expression of An Arabidopsis thaliana Transcription Factor AtPAP1

    Directory of Open Access Journals (Sweden)

    Pham Anh Tuan

    2014-08-01

    Full Text Available To improve the production of chlorogenic acid (CGA in hairy roots of Platycodon grandiflorum, we induced over-expression of Arabidopsis thaliana transcription factor production of anthocyanin pigment (AtPAP1 using an Agrobacterium rhizogenes-mediated transformation system. Twelve hairy root lines showing over-expression of AtPAP1 were generated. In order to investigate the regulation of AtPAP1 on the activities of CGA biosynthetic genes, the expression levels of seven P. grandiflorum CGA biosynthetic genes were analyzed in the hairy root line that had the greatest accumulation of AtPAP1 transcript, OxPAP1-1. The introduction of AtPAP1 increased the mRNA levels of all examined CGA biosynthetic genes and resulted in a 900% up-regulation of CGA accumulation in OxPAP1-1 hairy roots relative to controls. This suggests that P. grandiflorum hairy roots that over-express the AtPAP1 gene are a potential alternative source of roots for the production of CGA.

  4. Bcl-2 over-expression fails to prevent age-related loss of calretinin positive neurons in the mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Han Mingbo

    2006-08-01

    Full Text Available Abstract Background Cognitive performance declines with increasing age. Possible cellular mechanisms underlying this age-related functional decline remain incompletely understood. Early studies attributed this functional decline to age-related neuronal loss. Subsequent studies using unbiased stereological techniques found little or no neuronal loss during aging. However, studies using specific cellular markers found age-related loss of specific neuronal types. To test whether there is age-related loss of specific neuronal populations in the hippocampus, and subsequently, whether over-expression of the B-cell lymphoma protein-2 (Bcl-2 in these neurons could delay possible age-related neuronal loss, we examined calretinin (CR positive neurons in the mouse dentate gyrus during aging. Result In normal mice, there was an age-related loss of CR positive cells in the dentate gyrus. At the same region, there was no significant decrease of total numbers of neurons, which suggested that age-related loss of CR positive cells was due to the decrease of CR expression in these cells instead of cell death. In the transgenic mouse line over-expressing Bcl-2 in neurons, there was an age-related loss of CR positive cells. Interestingly, there was also an age-related neuronal loss in this transgenic mouse line. Conclusion These data suggest an age-related loss of CR positive neurons but not total neuronal loss in normal mice and this age-related neuronal change is not prevented by Bcl-2 over-expression.

  5. Over-expression of the mycobacterial trehalose-phosphate phosphatase OtsB2 results in a defect in macrophage phagocytosis associated with increased mycobacterial-macrophage adhesion

    Directory of Open Access Journals (Sweden)

    Hao Li

    2016-11-01

    Full Text Available Trehalose-6-phosphate phosphatase (OtsB2 is involved in the OtsAB trehalose synthesis pathway to produce free trehalose and is strictly essential for mycobacterial growth. We wished to determine the effects of OtsB2 expression on mycobacterial phenotypes such as growth, phagocytosis and survival in macrophages. Mycobacterium bovis-BCG (BCG over-expressing OtsB2 were able to better survive in stationary phase. Over-expression of OtsB2 led to a decrease in phagocytosis but not survival in THP-1 macrophage-like cells, and this was not due to a decrease in general macrophage phagocytic activity. Surprisingly, when we investigated macrophage-mycobacterial interactions by flow cytometry and atomic force microscopy, we discovered that BCG over-expressing OtsB2 have stronger binding to THP-1 cells than wild-type BCG. These results suggest that altering OtsB2 expression has implications for mycobacterial host-pathogen interactions. Macrophage-mycobacteria phagocytic interactions are complex and merit further study.

  6. Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: Insights on viral regulation of apoptosis and proliferation

    International Nuclear Information System (INIS)

    Yeung, Y.-S.; Yip, C.-W.; Hon, C.-C.; Chow, Ken Y.C.; Ma, Iris C.M.; Zeng Fanya; Leung, Frederick C.C.

    2008-01-01

    We have previously demonstrated that over-expression of spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) or its C-terminal subunit (S2) is sufficient to induce apoptosis in vitro. To further investigate the possible roles of S2 in SARS-CoV-induced apoptosis and pathogenesis of SARS, we characterized the host expression profiles induced upon S2 over-expression in Vero E6 cells by oligonucleotide microarray analysis. Possible activation of mitochondrial apoptotic pathway in S2 expressing cells was suggested, as evidenced by the up-regulation of cytochrome c and down-regulation of the Bcl-2 family anti-apoptotic members. Inhibition of Bcl-2-related anti-apoptotic pathway was further supported by the diminution of S2-induced apoptosis in Vero E6 cells over-expressing Bcl-xL. In addition, modulation of CCN E2 and CDKN 1A implied the possible control of cell cycle arrest at G1/S phase. This study is expected to extend our understanding on the pathogenesis of SARS at a molecular level

  7. Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

    2015-01-01

    Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

  8. Over-expression of TaMYB33 encoding a novel wheat MYB transcription factor increases salt and drought tolerance in Arabidopsis.

    Science.gov (United States)

    Qin, Yuxiang; Wang, Mengcheng; Tian, Yanchen; He, Wenxing; Han, Lu; Xia, Guangmin

    2012-06-01

    Salt and drought stresses often adversely affect plant growth and productivity, MYB transcription factors have been shown to participate in the response to these stresses. Here we identified a new R2R3-type MYB transcription factor gene TaMYB33 from wheat (Triticum aestivum). TaMYB33 was induced by NaCl, PEG and ABA treatments, and its promoter sequence contains putative ABRE, MYB and other abiotic stress related cis-elements. Ectopic over-expression of TaMYB33 in Arabidopsis thaliana remarkably enhanced its tolerance to drought and NaCl stresses, but not to LiCl and KCl treatments. The expressions of AtP5CS and AtZAT12 which mirror the activities of proline and ascorbate peroxidase synthesis respectively were induced in TaMYB33 over-expression lines, indicating TaMYB33 promotes the ability for osmotic pressure balance-reconstruction and reactive oxidative species (ROS) scavenging. The up-regulation of AtAAO3 along with down-regulation of AtABF3, AtABI1 in TaMYB33 over-expression lines indicated that ABA synthesis was elevated while its signaling was restricted. These results suggest that TaMYB33 enhances salt and drought tolerance partially through superior ability for osmotic balance reconstruction and ROS detoxification.

  9. Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Stacker Steven A

    2010-07-01

    Full Text Available Abstract Background It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. Methods We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3 and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. Results Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium, although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating

  10. The issue of multiple univariate comparisons in the context of neuroelectric brain mapping: an application in a neuromarketing experiment.

    Science.gov (United States)

    Vecchiato, G; De Vico Fallani, F; Astolfi, L; Toppi, J; Cincotti, F; Mattia, D; Salinari, S; Babiloni, F

    2010-08-30

    This paper presents some considerations about the use of adequate statistical techniques in the framework of the neuroelectromagnetic brain mapping. With the use of advanced EEG/MEG recording setup involving hundred of sensors, the issue of the protection against the type I errors that could occur during the execution of hundred of univariate statistical tests, has gained interest. In the present experiment, we investigated the EEG signals from a mannequin acting as an experimental subject. Data have been collected while performing a neuromarketing experiment and analyzed with state of the art computational tools adopted in specialized literature. Results showed that electric data from the mannequin's head presents statistical significant differences in power spectra during the visualization of a commercial advertising when compared to the power spectra gathered during a documentary, when no adjustments were made on the alpha level of the multiple univariate tests performed. The use of the Bonferroni or Bonferroni-Holm adjustments returned correctly no differences between the signals gathered from the mannequin in the two experimental conditions. An partial sample of recently published literature on different neuroscience journals suggested that at least the 30% of the papers do not use statistical protection for the type I errors. While the occurrence of type I errors could be easily managed with appropriate statistical techniques, the use of such techniques is still not so largely adopted in the literature. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  11. Lawrence Livermore National Laboratory Experience Using 30-Gallon Drum Neutron Multiplicity Counter for Measuring Plutonium-Bearing Salts

    International Nuclear Information System (INIS)

    Dearborn, D M; Keeton, S C

    2004-01-01

    Lawrence Livermore National Laboratory (LLNL) has been performing accountability measurements of plutonium (Pu) -bearing items with the 30-gallon drum neutron multiplicity counter (NMC) since August 1998. A previous paper focused on the LLNL experience with Pu-bearing oxide and metal items. This paper expands on the LLNL experience with Pu-bearing salts containing low masses of Pu. All Pu-bearing salts used in this study were measured using calorimetry and gamma isotopic analyses (Cal/Iso) as well as the 30-gallon drum NMC. The Cal/Iso values were treated as being the true measure of Pu content because of the inherent high accuracy of the Cal/Iso technique, even at low masses of Pu, when measured over a sufficient period of time. Unfortunately, the long time period required to achieve high accuracy from Cal/Iso can impact other required accountability measurements. The 30-gallon drum NMC is a much quicker system for making accountability measurements of a Pu-bearing salt and might be a desirable tradeoff. The accuracy of 30-gallon drum NMC measurements of Pu-bearing salts, relative to that of Cal/Iso, is presented in relation to the mass range and alpha associated with each item. Conclusions drawn from the use of the 30-gallon drum NMC for accountability measurements of salts are also included

  12. Suppression of cotton leaf curl disease symptoms in Gossypium hirsutum through over expression of host-encoded miRNAs.

    Science.gov (United States)

    Akmal, Mohd; Baig, Mirza S; Khan, Jawaid A

    2017-12-10

    Cotton leaf curl disease (CLCuD), a major factor resulting in the enormous yield losses in cotton crop, is caused by a distinct monopartite begomovirus in association with Cotton leaf curl Multan betasatellite (CLCuMB). Micro(mi)RNAs are known to regulate gene expression in eukaryotes, including antiviral defense in plants. In a previous study, we had computationally identified a set of cotton miRNAs, which were shown to have potential targets in the genomes of Cotton leaf curl Multan virus (CLCuMuV) and CLCuMB at multiple loci. In the current study, effect of Gossypium arboreum-encoded miRNAs on the genome of CLCuMuV and CLCuMB was investigated in planta. Two computationally predicted cotton-encoded miRNAs (miR398 and miR2950) that showed potential to bind multiple Open Reading Frames (ORFs; C1, C4, V1, and non- coding intergenic region) of CLCuMuV, and (βC1) of CLCuMB were selected. Functional validation of miR398 and miR2950 was done by overexpression approach in G. hirsutum var. HS6. A total of ten in vitro cotton plants were generated from independent events and subjected to biological and molecular analyses. Presence of the respective Precursor (pre)-miRNA was confirmed through PCR and Southern blotting, and their expression level was assessed by semi quantitative RT-PCR, Real Time quantitative PCR and northern hybridization in the PCR-positive lines. Southern hybridization revealed 2-4 copy integration of T-DNA in the genome of the transformed lines. Remarkably, expression of pre-miRNAs was shown up to 5.8-fold higher in the transgenic (T 0 ) lines as revealed by Real Time PCR. The virus resistance was monitored following inoculation of the transgenic cotton lines with viruliferous whitefly (Bemisia tabaci) insect vector. After inoculation, four of the transgenic lines remained apparently symptom free. While a very low titre of viral DNA could be detected by Rolling circle amplification, betasatellite responsible for symptom induction could not be detected

  13. Multiple plastic biliary stent placement in the management of large and multiple choledochal stones: single center experience and review of the literature.

    Science.gov (United States)

    Bektaş, Hasan; Gürbulak, Bünyamin; Şahin, Zeynep Deniz; Düzköylü, Yiğit; Çolak, Şükrü; Gürbulak, Esin Kabul; Güneş, Mehmet Emin; Çakar, Ekrem

    2017-09-01

    Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is the first step treatment modality of choledocholithiasis. In spite of an extended sphincterotomy, 10-15% of complex choledochal stones (larger than 15 mm and/or more than 3 stones) cannot be removed and recurrent ERCP procedures may be needed. To evaluate the role and efficiency of multiple biliary stent application in the treatment of large and multiple choledochal stones. Patients with complex choledochal stones and patients with inadequate choledochal clearance during ERCP were included in the study. The study group was divided into 2 groups as the placement of single (n = 27 patients) or multiple stents (n = 58 patients). After a mean time interval of 21 days (10-28), the ERCP procedure was tried for the second time and a stent was placed in case of recurrence. Successful biliary drainage was provided in both groups. The decrease in the longitudinal or transverse size of the stones after stent placement was found to be statistically significant in both groups (p = 0.001). Cholestatic enzymes (alkaline phosphatase (ALP), γ-glutamyltransferase (GGT)) and bilirubin levels decreased significantly in both groups following stenting (p = 0.001). Additionally, multiple stents functioned as a bridge starting from the first ERCP to full clearance in patients with large and multiple stones which could not be removed at once and saved them from the possible morbidities of an invasive operation. Endoscopic multiple biliary stent placement should be preferred in the treatment of patients with complex choledochal stones and high rates of co-morbidity, as a safe alternative to surgery.

  14. Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females

    Directory of Open Access Journals (Sweden)

    Emily M Perez-Torres

    2015-05-01

    Full Text Available Acute exposure to morphine after a traumatic event reduces trauma related symptoms in humans and conditioned fear expression in male rats. We aimed to determine whether acute administration of morphine alters consolidation of fear learning and extinction. Male and female rats in proestrus and metaestrus (high and low ovarian hormones respectively underwent fear conditioning and received saline or morphine (2.5 mg/kg s.c.. The next day they underwent extinction. Results showed increased freezing during extinction only in the morphine metaestrus group while morphine did not affect males or proestrus females. Recall of extinction was similar on all groups. On a second experiment, a subset of rats conditioned during metaestrus was administered morphine prior to extinction producing no effects. We then measured mu opioid receptor (MOR expression in the amygdala and periaqueductal gray (PAG at the end of extinction (day 2. In males and proestrus females, morphine caused an increase in MOR in the amygdala but no in the PAG. In metaestrus females, morphine did not change MOR expression in either structure. These data suggests that ovarian hormones may interact with MORs in the amygdala to transiently alter memory consolidation. Morphine given after trauma to females with low ovarian hormones might increase the recall of fear responses, making recovery harder.

  15. The experience of transitioning from relapsing remitting to secondary progressive multiple sclerosis: views of patients and health professionals.

    Science.gov (United States)

    O'Loughlin, Emer; Hourihan, Susan; Chataway, Jeremy; Playford, E Diane; Riazi, Afsane

    2017-09-01

    The majority of people with multiple sclerosis (pwMS) initially present with discreet periods of relapses followed by partial remission of symptoms (RRMS). Over time, most pwMS transition to secondary progressive MS (SPMS), characterized by a gradual accumulation of disability. This study aimed to explore the experiences, coping and needs associated with transitioning from RRMS to SPMS. Data were collected via semi-structured interviews with nine pwMS and seven specialist MS health professionals (HPs). Thematic analysis was used to analyze the data. Four major themes were identified: "Is this really happening?"; "Becoming a reality"; "A life of struggle"; and "Brushing oneself off and moving on." Findings suggested a process of moving from uncertainty towards confirmation of one's diagnostic label. Being reclassified with SPMS served as a turning point for many, and was accompanied by a range of cognitive, emotional and behavioral responses. The value of adequate information and support surrounding the transition, and the potential benefit of education and support for health professionals in relation to the transition were indicated. Understanding pwMS' experiences of the transition is essential if clinicians are to provide pwMS with appropriate support during the transition. Implications for Rehabilitation The timing and delivery of preparatory education for patients about the transition to SPMS should be carefully considered. Sufficient information and follow-up support following the reclassification of SPMS is crucial but sometimes lacking. The importance of sensitive communication of the reclassification of SPMS was highlighted. MS Specialist health professionals may potentially benefit from training and support around communication of the reclassification of SPMS. Given the potential negative psychological impact of the transition, the psychological wellbeing of the patients during the transition to SPMS should be monitored and responded to appropriately.

  16. Cloning and over expression of non-coding RNA rprA in E.coli and its resistance to Kanamycin without osmotic shock.

    Science.gov (United States)

    Sahni, Azita; Hajjari, Mohammadreza; Raheb, Jamshid; Foroughmand, Ali Mohammad; Asgari, Morteza

    2017-01-01

    Recent reports have indicated that small RNAs have key roles in the response of the E.coli to stress and also in the regulating of virulence factors. It seems that some small non-coding RNAs are involved in multidrug resistance. Previous studies have indicated that rprA can increase the tolerance to Kanamycin in RcsB-deficient Escherichia coli K-12 following osmotic shock. The current study aims to clone and over-express the non-coding RNA rprA in E.coli and investigate its effect on the bacterial resistance to Kanamycin without any osmotic shock. For this purpose, rprA gene was amplified by the PCR and then cloned into the PET-28a (+) vector. The recombinant plasmid was transformed into wild type E.coli BL21 (DE3). The over expression was induced by IPTG and confirmed by qRT-PCR. The resistance to the kanamycin was then measured in different times by spectrophotometry. The statistical analysis showed that the rprA can increase the resistance to Kanamycin in Ecoli K12. The interaction between rprA and rpoS was reviewed and analyzed by in silico methods. The results showed that the bacteria with over-expressed rprA were more resistant to Kanamycin. The present study is an important step to prove the role of non-coding RNA rprA in bacterial resistance. The data can be the basis for future works and can also help to develop and deliver next-generation antibiotics.

  17. Over-expression of 60s ribosomal L23a is associated with cellular proliferation in SAG resistant clinical isolates of Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Sanchita Das

    Full Text Available Sodium antimony gluconate (SAG unresponsiveness of Leishmania donovani (Ld had effectively compromised the chemotherapeutic potential of SAG. 60s ribosomal L23a (60sRL23a, identified as one of the over-expressed protein in different resistant strains of L.donovani as observed with differential proteomics studies indicates towards its possible involvement in SAG resistance in L.donovani. In the present study 60sRL23a has been characterized for its probable association with SAG resistance mechanism.The expression profile of 60s ribosomal L23a (60sRL23a was checked in different SAG resistant as well as sensitive strains of L.donovani clinical isolates by real-time PCR and western blotting and was found to be up-regulated in resistant strains. Ld60sRL23a was cloned, expressed in E.coli system and purified for raising antibody in swiss mice and was observed to have cytosolic localization in L.donovani. 60sRL23a was further over-expressed in sensitive strain of L.donovani to check its sensitivity profile against SAG (Sb V and III and was found to be altered towards the resistant mode.This study reports for the first time that the over expression of 60sRL23a in SAG sensitive parasite decreases the sensitivity of the parasite towards SAG, miltefosine and paramomycin. Growth curve of the tranfectants further indicated the proliferative potential of 60sRL23a assisting the parasite survival and reaffirming the extra ribosomal role of 60sRL23a. The study thus indicates towards the role of the protein in lowering and redistributing the drug pressure by increased proliferation of parasites and warrants further longitudinal study to understand the underlying mechanism.

  18. Measuring conditions and trends in ecosystem services at multiple scales: the Southern African Millennium Ecosystem Assessment (SAfMA) experience.

    Science.gov (United States)

    van Jaarsveld, A S; Biggs, R; Scholes, R J; Bohensky, E; Reyers, B; Lynam, T; Musvoto, C; Fabricius, C

    2005-02-28

    The Southern African Millennium Ecosystem Assessment (SAfMA) evaluated the relationships between ecosystem services and human well-being at multiple scales, ranging from local through to sub-continental. Trends in ecosystem services (fresh water, food, fuel-wood, cultural and biodiversity) over the period 1990-2000 were mixed across scales. Freshwater resources appear strained across the continent with large numbers of people not securing adequate supplies, especially of good quality water. This translates to high infant mortality patterns across the region. In some areas, the use of water resources for irrigated agriculture and urban-industrial expansion is taking place at considerable cost to the quality and quantity of freshwater available to ecosystems and for domestic use. Staple cereal production across the region has increased but was outstripped by population growth while protein malnutrition is on the rise. The much-anticipated wood-fuel crisis on the subcontinent has not materialized but some areas are experiencing shortages while numerous others remain vulnerable. Cultural benefits of biodiversity are considerable, though hard to quantify or track over time. Biodiversity resources remain at reasonable levels, but are declining faster than reflected in species extinction rates and appear highly sensitive to land-use decisions. The SAfMA sub-global assessment provided an opportunity to experiment with innovative ways to assess ecosystem services including the use of supply-demand surfaces, service sources and sink areas, priority areas for service provision, service 'hotspots' and trade-off assessments.

  19. Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4{sup +}CD25{sup +} regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Yulan; Purohit, Sharad [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, GA (United States); Chen, Xueqin; Yi, Bing [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); She, Jin-Xiong, E-mail: jshe@georgiahealth.edu [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, GA (United States)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer This is the first study to provide direct evidence of the role of Stat5b in NOD mice. Black-Right-Pointing-Pointer Over-expression of wild type Stat5b transgene protects NOD mice against diabetes. Black-Right-Pointing-Pointer This protection may be mediated by the up-regulation of CD4{sup +}CD25{sup +} Tregs. -- Abstract: The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4{sup +} T cells and especially CD8{sup +} T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4{sup +} and CD8{sup +} T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-{gamma}, TNF-{alpha} and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4{sup +}CD25{sup +} regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4{sup +}CD25{sup +} regulatory T cells.

  20. Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

    International Nuclear Information System (INIS)

    Guseva, Daria; Rizvanov, Albert A.; Salafutdinov, Ilnur I.; Kudryashova, Nezhdana V.; Palotás, András; Islamov, Rustem R.

    2014-01-01

    Highlights: • Gene and cell-based therapies comprise innovative aspects of regenerative medicine. • Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS. • Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords. • Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5. • Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. - Abstract: Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis

  1. Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guseva, Daria [Kazan State Medical University, Kazan, Republic of Tatarstan (Russian Federation); Hannover Medical School, Hannover (Germany); Rizvanov, Albert A.; Salafutdinov, Ilnur I.; Kudryashova, Nezhdana V. [Kazan Federal University, Kazan, Republic of Tatarstan (Russian Federation); Palotás, András, E-mail: palotas@asklepios-med.eu [Kazan Federal University, Kazan, Republic of Tatarstan (Russian Federation); Asklepios-Med (Private Medical Practice and Research Center), Szeged (Hungary); Islamov, Rustem R., E-mail: islamru@yahoo.com [Kazan State Medical University, Kazan, Republic of Tatarstan (Russian Federation)

    2014-09-05

    Highlights: • Gene and cell-based therapies comprise innovative aspects of regenerative medicine. • Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS. • Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords. • Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5. • Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. - Abstract: Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis.

  2. Over-expression of UDP-glycosyltransferase gene UGT2B17 is involved in chlorantraniliprole resistance in Plutella xylostella (L.).

    Science.gov (United States)

    Li, Xiuxia; Zhu, Bin; Gao, Xiwu; Liang, Pei

    2017-07-01

    UDP-glycosyltransferases (UGTs) are phase II detoxification enzymes widely distributed within living organisms. Their involvement in the biotransformation of various lipophilic endogenous compounds and phytoalexins in insects has been documented. However, the roles of this enzyme family in insecticide resistance have rarely been reported. Here, the functions of UGTs in chlorantraniliprole resistance in Plutella xylostella were investigated. Treatment with sulfinpyrazone and 5-nitrouracil (both inhibitors of UGT enzymes) significantly increased the toxicity of chlorantraniliprole against the third instar larvae of P. xylostella. Among the 23 UGT transcripts examined, only UGT2B17 was found to be over-expressed (with a range from 30.7- to 77.3-fold) in all four chlorantraniliprole-resistant populations compared to the susceptible one (CHS). The knock-down of UGT2B17 by RNA interference (RNAi) dramatically increased the toxicity of chlorantraniliprole by 27.4% and 29.8% in the CHS and CHR (resistant) populations, respectively. In contrast, exposure to phenobarbital significantly increased the relative expression of UGT2B17 while decreasing the toxicity of chlorantraniliprole to the larvae by 14.0%. UGT2B17 is involved in the detoxification of chlorantraniliprole, and its over-expression may play an important role in chlorantraniliprole resistance in P. xylostella. These results shed some light upon and further our understanding of the mechanisms of diamide insecticide resistance in insects. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  3. Over-Expression of Dopamine D2 Receptor and Inwardly Rectifying Potassium Channel Genes in Drug-Naive Schizophrenic Peripheral Blood Lymphocytes as Potential Diagnostic Markers

    Directory of Open Access Journals (Sweden)

    Ágnes Zvara

    2005-01-01

    Full Text Available Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3 was found to be over-expressed in schizophrenic PBL and proposed to be a diagnostic and follow-up marker for schizophrenia. In this study we screened PBL of 13 drug-naive/drug-free schizophrenic patients to identify additional markers of schizophrenia. One of the benefits of our study is the use of blood samples of non-medicated, drug-naive patients. This excludes the possibility that changes detected in gene expression levels might be attributed to the medication rather than to the disorder itself. Among others, genes for dopamine receptor D2 (DRD2 and the inwardly rectifying potassium channel (Kir2.3 were found to be over-expressed in microarray analysis. Increased mRNA levels were confirmed by quantitative real-time PCR (QRT-PCR using the SybrGreen method and dual labeled TaqMan probes. The use of both molecular markers allows a more rapid and precise prediction of schizophrenia and might help find the optimal medication for schizophrenic patients.

  4. Vesicular Trafficking Defects, Developmental Abnormalities, and Alterations in the Cellular Death Process Occur in Cell Lines that Over-Express Dictyostelium GTPase, Rab2, and Rab2 Mutants

    Directory of Open Access Journals (Sweden)

    Katherine Maringer

    2014-08-01

    Full Text Available Small molecular weight GTPase Rab2 has been shown to be a resident of pre-Golgi intermediates and required for protein transport from the ER to the Golgi complex, however, the function of Rab2 in Dictyostelium has yet to be fully characterized. Using cell lines that over-express DdRab2, as well as cell lines over-expressing constitutively active (CA, and dominant negative (DN forms of the GTPase, we report a functional role in vesicular transport specifically phagocytosis, and endocytosis. Furthermore, Rab2 like other GTPases cycles between an active GTP-bound and an inactive GDP-bound state. We found that this GTP/GDP cycle for DdRab2 is crucial for normal Dictyostelium development and cell–cell adhesion. Similar to Rab5 and Rab7 in C. elegans, we found that DdRab2 plays a role in programmed cell death, possibly in the phagocytic removal of apoptotic corpses.

  5. Over-expression of Arabidopsis thaliana SFD1/GLY1, the gene encoding plastid localized glycerol-3-phosphate dehydrogenase, increases plastidic lipid content in transgenic rice plants.

    Science.gov (United States)

    Singh, Vijayata; Singh, Praveen Kumar; Siddiqui, Adnan; Singh, Subaran; Banday, Zeeshan Zahoor; Nandi, Ashis Kumar

    2016-03-01

    Lipids are the major constituents of all membranous structures in plants. Plants possess two pathways for lipid biosynthesis: the prokaryotic pathway (i.e., plastidic pathway) and the eukaryotic pathway (i.e., endoplasmic-reticulum (ER) pathway). Whereas some plants synthesize galactolipids from diacylglycerol assembled in the plastid, others, including rice, derive their galactolipids from diacylglycerols assembled by the eukaryotic pathway. Arabidopsis thaliana glycerol-3-phosphate dehydrogenase (G3pDH), coded by SUPPRESSOR OF FATTY ACID DESATURASE 1 (SFD1; alias GLY1) gene, catalyzes the formation of glycerol 3-phosphate (G3p), the backbone of many membrane lipids. Here SFD1 was introduced to rice as a transgene. Arabidopsis SFD1 localizes in rice plastids and its over-expression increases plastidic membrane lipid content in transgenic rice plants without any major impact on ER lipids. The results suggest that over-expression of plastidic G3pDH enhances biosynthesis of plastid-localized lipids in rice. Lipid composition in the transgenic plants is consistent with increased phosphatidylglycerol synthesis in the plastid and increased galactolipid synthesis from diacylglycerol produced via the ER pathway. The transgenic plants show a higher photosynthetic assimilation rate, suggesting a possible application of this finding in crop improvement.

  6. Contextualized perceptions of movement as a source of expanded insight: People with multiple sclerosis' experience with physiotherapy.

    Science.gov (United States)

    Normann, Britt; Sørgaard, Knut W; Salvesen, Rolf; Moe, Siri

    2013-01-01

    The hospitals' outpatient clinics for people with multiple sclerosis (PwMS) are important in the health care. Research regarding physiotherapy in such clinics is limited. The purpose was to investigate how PwMS perceive movement during single sessions of physiotherapy in a hospital's outpatient clinic, and what do these experiences mean for the patient's insight into their movement disturbances? Qualitative research interviews were performed with a purposive sample of 12 PwMS and supplemented with seven videotaped sessions. Content analysis was performed. The results indicate that contextualized perceptions of movement appear to be an essential source for PwMS to gain expanded insight with regard to their individual movement disturbances regardless of their ambulatory status. The contextualization implies that perceptions of movement are integrated with the physiotherapist's explanations regarding optimizing gait and balance or other activities of daily life. Perceptions of improvement in body part movement and/or functional activities are vital to enhancing their understanding of their individual movement disorders, and they may provide expanded insight regarding future possibilities and limitations involving everyday tasks. The implementation of movements, which transforms the perceived improvement into self-assisted exercises, appeared to be meaningful. Contextualized perceptions of improvements in movement may strengthen the person's sense of ownership and sense of agency and thus promote autonomy and self-encouragement. The findings underpin the importance of contextualized perceptions of movement based on exploration of potential for change, as an integrated part of information and communication in the health care for PwMS. Further investigations are necessary to deepen our knowledge.

  7. Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

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    Mennerich Detlev

    2007-01-01

    Full Text Available Abstract Background Stromelysin-3 (ST-3 is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. Methods The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Results Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. Conclusion These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated "early stage" breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour

  8. Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

    International Nuclear Information System (INIS)

    Kasper, Grit; Lehmann, Kerstin E; Reule, Matthias; Tschirschmann, Miriam; Dankert, Niels; Stout-Weider, Karen; Lauster, Roland; Schrock, Evelin; Mennerich, Detlev; Duda, Georg N

    2007-01-01

    Stromelysin-3 (ST-3) is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated 'early stage' breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour fibroblasts leads to the stimulation of the IGF-1R pathway in

  9. Experiences in conducting multiple community-based HIV prevention trials among women in KwaZulu-Natal, South Africa

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    Moodley Jothi

    2010-04-01

    Full Text Available Abstract Background South Africa, with its scientific capacity, good infrastructure and high HIV incidence rates, is ideally positioned to conduct large-scale HIV prevention trials. The HIV Prevention Research Unit of the South African Medical Research Council conducted four phase III and one phase IIb trials of women-initiated HIV prevention options in KwaZulu-Natal between 2003 and 2009. A total of 7046 women participated, with HIV prevalence between 25% and 45% and HIV incidence ranging from 4.5-9.1% per year. Unfortunately none of the interventions tested had any impact on reducing the risk of HIV acquisition; however, extremely valuable experience was gained, lessons learned and capacity built, while the communities gained associated benefits. Experience Our experience in conducting these trials ranged from setting up community partnerships to developing clinical research sites and dissemination of trial results. Community engagement included setting up community-based research sites with approval from both political and traditional leaders, and developing community advisory groups to assist with the research process. Community-wide education on HIV/sexually transmitted infection prevention, treatment and care was provided to over 90 000 individuals. Myths and misconceptions were addressed through methods such as anonymous suggestion boxes in clinic waiting areas and intensive education and counselling. Attempts were made to involve male partners to foster support and facilitate recruitment of women. Peer educator programmes were initiated to provide ongoing education and also to facilitate recruitment of women to the trials. Recruitment strategies such as door-to-door recruitment and community group meetings were initiated. Over 90% of women enrolled were retained. Community benefits from the trial included education on HIV prevention, treatment and care and provision of ancillary care (such as Pap smears, reproductive health care and

  10. Tocopherol levels in different mango varieties correlate with MiHPPD expression and its over-expression elevates tocopherols in transgenic Arabidopsis and tomato.

    Science.gov (United States)

    Singh, Rajesh K; Chaurasia, Akhilesh K; Bari, Rupesh; Sane, Vidhu A

    2017-10-01

    Mango fruit tocopherol levels vary in different varieties during ripening. This study shows that tocopherol accumulation is highly correlated with its p-hydroxyphenyl pyruvate dioxygenase ( MiHPPD ) gene expression during ripening. MiHPPD transcript is ethylene induced and differentially expressed in four mango varieties used in this study. Higher/lower accumulation of tocopherol (mainly α-tocopherol) was achieved by heterologous expression of MiHPPD in Arabidopsis and tomato. The results suggest that tocopherol accumulation in mango fruit is correlated to MiHPPD gene expression. Over-expression of MiHPPD gene channelizes the flux towards tocophreol biosynthesis and could be used as a potential tool for metabolic engineering.

  11. Over-expression of a tobacco nitrate reductase gene in wheat (Triticum aestivum L. increases seed protein content and weight without augmenting nitrogen supplying.

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    Xiao-Qiang Zhao

    Full Text Available Heavy nitrogen (N application to gain higher yield of wheat (Triticum aestivum L. resulted in increased production cost and environment pollution. How to diminish the N supply without losing yield and/or quality remains a challenge. To meet the challenge, we integrated and expressed a tobacco nitrate reductase gene (NR in transgenic wheat. The 35S-NR gene was transferred into two winter cultivars, "Nongda146" and "Jimai6358", by Agrobacterium-mediation. Over-expression of the transgene remarkably enhanced T1 foliar NR activity and significantly augmented T2 seed protein content and 1000-grain weight in 63.8% and 68.1% of T1 offspring (total 67 individuals analyzed, respectively. Our results suggest that constitutive expression of foreign nitrate reductase gene(s in wheat might improve nitrogen use efficiency and thus make it possible to increase seed protein content and weight without augmenting N supplying.

  12. Over-expression of a tobacco nitrate reductase gene in wheat (Triticum aestivum L.) increases seed protein content and weight without augmenting nitrogen supplying.

    Science.gov (United States)

    Zhao, Xiao-Qiang; Nie, Xuan-Li; Xiao, Xing-Guo

    2013-01-01

    Heavy nitrogen (N) application to gain higher yield of wheat (Triticum aestivum L.) resulted in increased production cost and environment pollution. How to diminish the N supply without losing yield and/or quality remains a challenge. To meet the challenge, we integrated and expressed a tobacco nitrate reductase gene (NR) in transgenic wheat. The 35S-NR gene was transferred into two winter cultivars, "Nongda146" and "Jimai6358", by Agrobacterium-mediation. Over-expression of the transgene remarkably enhanced T1 foliar NR activity and significantly augmented T2 seed protein content and 1000-grain weight in 63.8% and 68.1% of T1 offspring (total 67 individuals analyzed), respectively. Our results suggest that constitutive expression of foreign nitrate reductase gene(s) in wheat might improve nitrogen use efficiency and thus make it possible to increase seed protein content and weight without augmenting N supplying.

  13. RNAi and Homologous Over-Expression Based Functional Approaches Reveal Triterpenoid Synthase Gene-Cycloartenol Synthase Is Involved in Downstream Withanolide Biosynthesis in Withania somnifera.

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    Smrati Mishra

    Full Text Available Withania somnifera Dunal, is one of the most commonly used medicinal plant in Ayurvedic and indigenous medicine traditionally owing to its therapeutic potential, because of major chemical constituents, withanolides. Withanolide biosynthesis requires the activities of several enzymes in vivo. Cycloartenol synthase (CAS is an important enzyme in the withanolide biosynthetic pathway, catalyzing cyclization of 2, 3 oxidosqualene into cycloartenol. In the present study, we have cloned full-length WsCAS from Withania somnifera by homology-based PCR method. For gene function investigation, we constructed three RNAi gene-silencing constructs in backbone of RNAi vector pGSA and a full-length over-expression construct. These constructs were transformed in Agrobacterium strain GV3101 for plant transformation in W. somnifera. Molecular and metabolite analysis was performed in putative Withania transformants. The PCR and Southern blot results showed the genomic integration of these RNAi and overexpression construct(s in Withania genome. The qRT-PCR analysis showed that the expression of WsCAS gene was considerably downregulated in stable transgenic silenced Withania lines compared with the non-transformed control and HPLC analysis showed that withanolide content was greatly reduced in silenced lines. Transgenic plants over expressing CAS gene displayed enhanced level of CAS transcript and withanolide content compared to non-transformed controls. This work is the first full proof report of functional validation of any metabolic pathway gene in W. somnifera at whole plant level as per our knowledge and it will be further useful to understand the regulatory role of different genes involved in the biosynthesis of withanolides.

  14. Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells

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    Hisatomi Keiko

    2012-06-01

    Full Text Available Abstract Background Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF. We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF-β1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro. Methods The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-β1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining. Results TGF-β1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-β1. Conclusion We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition.

  15. Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

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    John P. Collister

    2014-12-01

    Full Text Available The brain senses circulating levels of angiotensin II (AngII via circumventricular organs, such as the subfornical organ (SFO, and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD, an intracellular superoxide (O2·− scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·− in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD or control vector (AdEmpty were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min for ten days. Rats over-expressing CuZnSOD (n = 7 in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9. These results support the hypothesis that production of O2·− in the MnPO contributes to the development of chronic AngII-dependent hypertension.

  16. Prerequisite for highly efficient isoprenoid production by cyanobacteria discovered through the over-expression of 1-deoxy-d-xylulose 5-phosphate synthase and carbon allocation analysis.

    Science.gov (United States)

    Kudoh, Kai; Kawano, Yusuke; Hotta, Shingo; Sekine, Midori; Watanabe, Takafumi; Ihara, Masaki

    2014-07-01

    Cyanobacteria have recently been receiving considerable attention owing to their potential as photosynthetic producers of biofuels and biomaterials. Here, we focused on the production of isoprenoids by cyanobacteria, and aimed to provide insight into metabolic engineering design. To this end, we examined the over-expression of a key enzyme in 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, 1-deoxy-d-xylulose 5-phosphate synthase (DXS) in the cyanobacterium Synechocystis sp. PCC6803. In the DXS-over-expression strain (Dxs_ox), the mRNA and protein levels of DXS were 4-times and 1.5-times the levels in the wild-type (WT) strain, respectively. The carotenoid content of the Dxs_ox strain (8.4 mg/g dry cell weight [DCW]) was also up to 1.5-times higher than that in the WT strain (5.6 mg/g DCW), whereas the glycogen content dramatically decreased to an undetectable level. These observations suggested that the carotenoid content in the Dxs_ox strain was increased by consuming glycogen, which is a C-storage compound in cyanobacteria. We also quantified the total sugar (145 and 104 mg/g DCW), total fatty acids (31 and 24 mg/g DCW) and total protein (200 and 240 mg/g DCW) content in the WT and Dxs_ox strains, respectively, which were much higher than the carotenoid content. In particular, approximately 54% of the proteins were phycobiliproteins. This study demonstrated the major destinations of carbon flux in cyanobacteria, and provided important insights into metabolic engineering. Target yield can be improved through optimization of gene expression, the DXS protein stabilization, cell propagation depression and restriction of storage compound synthesis. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of Regenerating Gene (REG protein in fulminant type 1 diabetes.

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    Kaoru Aida

    Full Text Available BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs, extracellular matrix (ECM, and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. RESULT: Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. CONCLUSION: The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.

  18. Multiple acquisition of magic angle spinning solid-state NMR experiments using one receiver: Application to microcrystalline and membrane protein preparations

    Science.gov (United States)

    Gopinath, T.; Veglia, Gianluigi

    2015-04-01

    Solid-state NMR spectroscopy of proteins is a notoriously low-throughput technique. Relatively low-sensitivity and poor resolution of protein samples require long acquisition times for multidimensional NMR experiments. To speed up data acquisition, we developed a family of experiments called Polarization Optimized Experiments (POE), in which we utilized the orphan spin operators that are discarded in classical multidimensional NMR experiments, recovering them to allow simultaneous acquisition of multiple 2D and 3D experiments, all while using conventional probes with spectrometers equipped with one receiver. POE allow the concatenation of multiple 2D or 3D pulse sequences into a single experiment, thus potentially combining all of the aforementioned advances, boosting the capability of ssNMR spectrometers at least two-fold without the addition of any hardware. In this perspective, we describe the first generation of POE, such as dual acquisition MAS (or DUMAS) methods, and then illustrate the evolution of these experiments into MEIOSIS, a method that enables the simultaneous acquisition of multiple 2D and 3D spectra. Using these new pulse schemes for the solid-state NMR investigation of biopolymers makes it possible to obtain sequential resonance assignments, as well as distance restraints, in about half the experimental time. While designed for acquisition of heteronuclei, these new experiments can be easily implemented for proton detection and coupled with other recent advancements, such as dynamic nuclear polarization (DNP), to improve signal to noise. Finally, we illustrate the application of these methods to microcrystalline protein preparations as well as single and multi-span membrane proteins reconstituted in lipid membranes.

  19. Item difficulty of multiple choice tests dependant on different item response formats – An experiment in fundamental research on psychological assessment

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    KLAUS D. KUBINGER

    2007-12-01

    Full Text Available Multiple choice response formats are problematical as an item is often scored as solved simply because the test-taker is a lucky guesser. Instead of applying pertinent IRT models which take guessing effects into account, a pragmatic approach of re-conceptualizing multiple choice response formats to reduce the chance of lucky guessing is considered. This paper compares the free response format with two different multiple choice formats. A common multiple choice format with a single correct response option and five distractors (“1 of 6” is used, as well as a multiple choice format with five response options, of which any number of the five is correct and the item is only scored as mastered if all the correct response options and none of the wrong ones are marked (“x of 5”. An experiment was designed, using pairs of items with exactly the same content but different response formats. 173 test-takers were randomly assigned to two test booklets of 150 items altogether. Rasch model analyses adduced a fitting item pool, after the deletion of 39 items. The resulting item difficulty parameters were used for the comparison of the different formats. The multiple choice format “1 of 6” differs significantly from “x of 5”, with a relative effect of 1.63, while the multiple choice format “x of 5” does not significantly differ from the free response format. Therefore, the lower degree of difficulty of items with the “1 of 6” multiple choice format is an indicator of relevant guessing effects. In contrast the “x of 5” multiple choice format can be seen as an appropriate substitute for free response format.

  20. Developing a questionnaire on physical activity support of people with (profound) intellectual (and multiple) disabilities : Experiences from the Netherlands

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2017-01-01

    Introduction: People with intellectual disabilities (ID) undertake extremely low levels of physical activity, which is even more true in people with profound intellectual and multiple disabilities (PIMD). Physical activity approaches, particularly for people with PIMD, are more likely to be

  1. What about False Insights? Deconstructing the Aha! Experience along Its Multiple Dimensions for Correct and Incorrect Solutions Separately

    Science.gov (United States)

    Danek, Amory H.; Wiley, Jennifer

    2017-01-01

    The subjective Aha! experience that problem solvers often report when they find a solution has been taken as a marker for insight. If Aha! is closely linked to insightful solution processes, then theoretically, an Aha! should only be experienced when the correct solution is found. However, little work has explored whether the Aha! experience can also accompany incorrect solutions (“false insights”). Similarly, although the Aha! experience is not a unitary construct, little work has explored the different dimensions that have been proposed as its constituents. To address these gaps in the literature, 70 participants were presented with a set of difficult problems (37 magic tricks), and rated each of their solutions for Aha! as well as with regard to Suddenness in the emergence of the solution, Certainty of being correct, Surprise, Pleasure, Relief, and Drive. Solution times were also used as predictors for the Aha! experience. This study reports three main findings: First, false insights exist. Second, the Aha! experience is multidimensional and consists of the key components Pleasure, Suddenness and Certainty. Third, although Aha! experiences for correct and incorrect solutions share these three common dimensions, they are also experienced differently with regard to magnitude and quality, with correct solutions emerging faster, leading to stronger Aha! experiences, and higher ratings of Pleasure, Suddenness, and Certainty. Solution correctness proffered a slightly different emotional coloring to the Aha! experience, with the additional perception of Relief for correct solutions, and Surprise for incorrect ones. These results cast some doubt on the assumption that the occurrence of an Aha! experience can serve as a definitive signal that a true insight has taken place. On the other hand, the quantitative and qualitative differences in the experience of correct and incorrect solutions demonstrate that the Aha! experience is not a mere epiphenomenon. Strong Aha

  2. The Effects of Brand Experiences on Quality, Satisfaction and Loyalty: An Empirical Study in the Telecommunications Multiple-play Service Market

    Directory of Open Access Journals (Sweden)

    António Carrizo Moreira

    2017-03-01

    Full Text Available This article seeks to add to the body of knowledge on the role played by brand experience and its relationship with satisfaction, trust and service quality in the development of loyalty. Structural Equation Modelling (sem is used to analyze 690 telecommunications multiple-play users in the Portuguese telecommunications market. Our conclusions show that brand experiences can be used to generate loyalty, trust and quality perceptions; although satisfaction was confirmed to be the main loyalty predictor, service quality has an important indirect effect. In order to build customer loyalty, marketers must manage brand experiences, service quality, satisfaction and trust. Brand experiences can be explored as a way to differentiate services, to change customers’ perceptions toward a brand and, ultimately, lead to customer retention. Furthermore, providing reliable services is of the utmost importance for service providers.

  3. The effect of human factor H on immunogenicity of meningococcal native outer membrane vesicle vaccines with over-expressed factor H binding protein.

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    Peter T Beernink

    Full Text Available The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH, is fH-binding protein (fHbp, which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001 and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003. By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002, and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001. Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans.

  4. Over-Expression of the Pikh Gene with a CaMV 35S Promoter Leads to Improved Blast Disease (Magnaporthe oryzae) Tolerance in Rice

    Science.gov (United States)

    Azizi, Parisa; Rafii, Mohd Y.; Abdullah, Siti N. A.; Hanafi, Mohamed M.; Maziah, M.; Sahebi, Mahbod; Ashkani, Sadegh; Taheri, Sima; Jahromi, Mohammad F.

    2016-01-01

    Magnaporthe oryzae is a rice blast fungus and plant pathogen that causes a serious rice disease and, therefore, poses a threat to the world's second most important food security crop. Plant transformation technology has become an adaptable system for cultivar improvement and to functionally analyze genes in plants. The objective of this study was to determine the effects (through over-expressing and using the CaMV 35S promoter) of Pikh on MR219 resistance because it is a rice variety that is susceptible to the blast fungus pathotype P7.2. Thus, a full DNA and coding DNA sequence (CDS) of the Pikh gene, 3172 bp, and 1206 bp in length, were obtained through amplifying the gDNA and cDNA template from a PH9-resistant rice variety using a specific primer. Agrobacterium-mediated transformation technology was also used to introduce the Pikh gene into the MR219 callus. Subsequently, transgenic plants were evaluated from the DNA to protein stages using polymerase chain reaction (PCR), semi-quantitative RT-PCR, real-time quantitative PCR and high performance liquid chromatography (HPLC). Transgenic plants were also compared with a control using a real-time quantification technique (to quantify the pathogen population), and transgenic and control plants were challenged with the local most virulent M. oryzae pathotype, P7.2. Based on the results, the Pikh gene encodes a hydrophilic protein with 18 sheets, 4 helixes, and 21 coils. This protein contains 401 amino acids, among which the amino acid sequence from 1 to 376 is a non-cytoplasmic region, that from 377 to 397 is a transmembrane region, and that from 398 to 401 is a cytoplasmic region with no identified disordered regions. The Pikh gene was up-regulated in the transgenic plants compared with the control plants. The quantity of the amino acid leucine in the transgenic rice plants increased significantly from 17.131 in the wild-type to 47.865 mg g−1 in transgenic plants. The M. oryzae population was constant at 31, 48

  5. Over-Expression of the Pikh Gene with a CaMV 35S Promoter Leads to Improved Blast Disease (Magnaporthe oryzae) Tolerance in Rice.

    Science.gov (United States)

    Azizi, Parisa; Rafii, Mohd Y; Abdullah, Siti N A; Hanafi, Mohamed M; Maziah, M; Sahebi, Mahbod; Ashkani, Sadegh; Taheri, Sima; Jahromi, Mohammad F

    2016-01-01

    Magnaporthe oryzae is a rice blast fungus and plant pathogen that causes a serious rice disease and, therefore, poses a threat to the world's second most important food security crop. Plant transformation technology has become an adaptable system for cultivar improvement and to functionally analyze genes in plants. The objective of this study was to determine the effects (through over-expressing and using the CaMV 35S promoter) of Pikh on MR219 resistance because it is a rice variety that is susceptible to the blast fungus pathotype P7.2. Thus, a full DNA and coding DNA sequence (CDS) of the Pikh gene, 3172 bp, and 1206 bp in length, were obtained through amplifying the gDNA and cDNA template from a PH9-resistant rice variety using a specific primer. Agrobacterium-mediated transformation technology was also used to introduce the Pikh gene into the MR219 callus. Subsequently, transgenic plants were evaluated from the DNA to protein stages using polymerase chain reaction (PCR), semi-quantitative RT-PCR, real-time quantitative PCR and high performance liquid chromatography (HPLC). Transgenic plants were also compared with a control using a real-time quantification technique (to quantify the pathogen population), and transgenic and control plants were challenged with the local most virulent M. oryzae pathotype, P7.2. Based on the results, the Pikh gene encodes a hydrophilic protein with 18 sheets, 4 helixes, and 21 coils. This protein contains 401 amino acids, among which the amino acid sequence from 1 to 376 is a non-cytoplasmic region, that from 377 to 397 is a transmembrane region, and that from 398 to 401 is a cytoplasmic region with no identified disordered regions. The Pikh gene was up-regulated in the transgenic plants compared with the control plants. The quantity of the amino acid leucine in the transgenic rice plants increased significantly from 17.131 in the wild-type to 47.865 mg g(-1) in transgenic plants. The M. oryzae population was constant at 31, 48

  6. College Alcohol Beliefs and Drinking Consequences: A Multiple Mediation Analysis of Norms, Expectancies, and Willingness to Experience Drinking Consequences

    Science.gov (United States)

    Osberg, Timothy M.; Boyer, Amber

    2018-01-01

    Objective: We explored the potential mediating role of willingness to experience drinking consequences and other traditional alcohol outcome predictors (descriptive norms, injunctive norms, positive alcohol expectancies) in explaining the association between college alcohol beliefs1 (CABs) and the actual experience of drinking consequences among…

  7. Experiments and Simulations of the Use of Time-Correlated Thermal Neutron Counting to Determine the Multiplication of an Assembly of Highly Enriched Uranium

    Energy Technology Data Exchange (ETDEWEB)

    David L. Chichester; Mathew T. Kinlaw; Scott M. Watson; Jeffrey M. Kalter; Eric C. Miller; William A. Noonan

    2014-11-01

    A series of experiments and numerical simulations using thermal-neutron time-correlated measurements has been performed to determine the neutron multiplication, M, of assemblies of highly enriched uranium available at Idaho National Laboratory. The experiments used up to 14.4 kg of highly-enriched uranium, including bare assemblies and assemblies reflected with high-density polyethylene, carbon steel, and tungsten. A small 252Cf source was used to initiate fission chains within the assembly. Both the experiments and the simulations used 6-channel and 8-channel detector systems, each consisting of 3He proportional counters moderated with polyethylene; data was recorded in list mode for analysis. 'True' multiplication values for each assembly were empirically derived using basic neutron production and loss values determined through simulation. A total of one-hundred and sixteen separate measurements were performed using fifty-seven unique measurement scenarios, the multiplication varied from 1.75 to 10.90. This paper presents the results of these comparisons and discusses differences among the various cases.

  8. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  9. A novel approach for over-expression, characterization, and isotopic enrichment of a homogeneous species of acyl carrier protein from Plasmodium falciparum

    International Nuclear Information System (INIS)

    Sharma, Shailendra Kumar; Modak, Rahul; Sharma, Shilpi; Sharma, Alok Kumar; Sarma, Siddhartha P.; Surolia, Avadhesha; Surolia, Namita

    2005-01-01

    Acyl carrier protein (ACP) plays a central role in fatty acid biosynthesis by transferring the acyl groups from one enzyme to another for the completion of the fatty acid synthesis cycle. Holo-ACP is the obligatory substrate for the synthesis of acyl-ACPs which act as the carrier and donor for various metabolic reactions. Despite its interactions with numerous proteins in the cell, its mode of interaction is poorly understood. Here, we report the over-expression of PfACP in minimal medium solely in its holo form and in high yield. Expression in minimal media provides a means to isotopically label PfACP for high resolution multi-nuclear and multi-dimensional NMR studies. Indeed, the proton-nitrogen correlated NMR spectrum exhibits very high chemical shift dispersion and resolution. We also show that holo-PfACP thus expressed is amenable to acylation reactions using Escherichia coli acyl-ACP synthetase as well as by standard chemical methods

  10. Comparative Study on Growth Performance of Transgenic (Over-Expressed OsNHX1 and Wild-Type Nipponbare under Different Salinity Regimes

    Directory of Open Access Journals (Sweden)

    Nurul Kahrani ISHAK

    2015-11-01

    Full Text Available Transgenic Nipponbare which over-expressed a Na+/H+ antiporter gene OsNHX1 was used to compare its growth performance, water status and photosynthetic efficiency with its wild type under varying salinity regimes. Chlorophyll content, quantum yield and photosynthetic rate were measured to assess the impact of salinity stress on photosynthetic efficiency for transgenic and wild-type Nipponbare. Effects of salinity on water status and gas exchange to both lines were studied by measuring water use efficiency, instantaneous transpiration rate and stomatal conductance. Dry shoot weight and leaf area were determined after three months of growth to assess the impacts of salinity on the growth of those two lines. Our study showed that both lines were affected by salinity stress, however, the transgenic line showed higher photosynthetic efficiency, better utilization of water, and better growth due to low transpiration rate and stomatal conductance. Reduction of photosynthetic efficiency exhibited by the wild-type Nipponbare was correlated to its poor growth under salinity stress.

  11. TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties.

    Directory of Open Access Journals (Sweden)

    Barbara Deracinois

    Full Text Available Although the physiological properties of the blood-brain barrier (BBB are relatively well known, the phenotype of the component brain capillary endothelial cells (BCECs has yet to be described in detail. Likewise, the molecular mechanisms that govern the establishment and maintenance of the BBB are largely unknown. Proteomics can be used to assess quantitative changes in protein levels and identify proteins involved in the molecular pathways responsible for cellular differentiation. Using the well-established in vitro BBB model developed in our laboratory, we performed a differential nano-LC MALDI-TOF/TOF-MS study of Triton X-100-soluble protein species from bovine BCECs displaying either limited BBB functions or BBB functions re-induced by glial cells. Due to the heterogeneity of the crude extract, we increased identification yields by applying a repeatable, reproducible fractionation process based on the proteins' relative hydrophobicity. We present proteomic and biochemical evidence to show that tissue non-specific alkaline phosphatase (TNAP and Eps15 homology domain-containing protein 1(EDH1 are over-expressed by bovine BCECs after the re-induction of BBB properties. We discuss the impact of these findings on current knowledge of endothelial and BBB permeability.

  12. Lysophosphatidic acid activates peroxisome proliferator activated receptor-γ in CHO cells that over-express glycerol 3-phosphate acyltransferase-1.

    Directory of Open Access Journals (Sweden)

    Cliona M Stapleton

    2011-04-01

    Full Text Available Lysophosphatidic acid (LPA is an agonist for peroxisome proliferator activated receptor-γ (PPARγ. Although glycerol-3-phosphate acyltransferase-1 (GPAT1 esterifies glycerol-3-phosphate to form LPA, an intermediate in the de novo synthesis of glycerolipids, it has been assumed that LPA synthesized by this route does not have a signaling role. The availability of Chinese Hamster Ovary (CHO cells that stably overexpress GPAT1, allowed us to analyze PPARγ activation in the presence of LPA produced as an intracellular intermediate. LPA levels in CHO-GPAT1 cells were 6-fold higher than in wild-type CHO cells, and the mRNA abundance of CD36, a PPARγ target, was 2-fold higher. Transactivation assays showed that PPARγ activity was higher in the cells that overexpressed GPAT1. PPARγ activity was enhanced further in CHO-GPAT1 cells treated with the PPARγ ligand troglitazone. Extracellular LPA, phosphatidic acid (PA or a membrane-permeable diacylglycerol had no effect, showing that PPARγ had been activated by LPA generated intracellularly. Transient transfection of a vector expressing 1-acylglycerol-3-phosphate acyltransferase-2, which converts endogenous LPA to PA, markedly reduced PPARγ activity, as did over-expressing diacylglycerol kinase, which converts DAG to PA, indicating that PA could be a potent inhibitor of PPARγ. These data suggest that LPA synthesized via the glycerol-3-phosphate pathway can activate PPARγ and that intermediates of de novo glycerolipid synthesis regulate gene expression.

  13. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

    Directory of Open Access Journals (Sweden)

    Ohlemiller Kevin K

    2010-07-01

    Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

  14. Enhanced hyluronic acid production in Streptococcus zooepidemicus by over expressing HasA and molecular weight control with Niscin and glucose

    Directory of Open Access Journals (Sweden)

    Alireza Zakeri

    2017-12-01

    Full Text Available Hyaluronic acid (HA is a high molecular weight linear polysaccharide, endowed with unique physiological and biological properties. Given its unique properties, HA have unprecedented applications in the fields of medicine and cosmetics. The ever growing demand for HA production is the driving force behind the need for finding and developing novel and amenable sources of the HA producers. Microbial fermentation of Streptococcus zooepidemicus deemed as one the most expeditious and pervasive methods of HA production. Herein, a wild type Streptococcus zooepidemicus, intrinsically expressing high levels of HA, was selected and optimized for HA production. HasA gene was amplified and introduced into the wild type Streptococcus zooepidemicus, under the control of Nisin promoter. The HasA over-expression increased the HA production, while the molecular weight was decreased. In order to compensate for molecular weight loss, the glucose concentration was increased to an optimum amount of 90 g/L. It is hypostatizes that excess glucose would rectify the distribution of the monomers and each HasA molecule would be provided with sufficient amount of substrates to lengthen the HA molecules. Arriving at an improved strain and optimized cultivating condition would pave the way for industrial grade HA production with high quality and quantity. Keywords: Streptococcus zooepidemicus, Hyaluronic acid, HasA, Glucose, Molecular weight

  15. Measuring conditions and trends in ecosystem services at multiple scales: the Southern African Millennium Ecosystem Assessment (SAfMA) experience

    OpenAIRE

    van Jaarsveld, A.S; Biggs, R; Scholes, R.J; Bohensky, E; Reyers, B; Lynam, T; Musvoto, C; Fabricius, C

    2005-01-01

    The Southern African Millennium Ecosystem Assessment (SAfMA) evaluated the relationships between ecosystem services and human well-being at multiple scales, ranging from local through to sub-continental. Trends in ecosystem services (fresh water, food, fuel-wood, cultural and biodiversity) over the period 1990-2000 were mixed across scales. Freshwater resources appear strained across the continent with large numbers of people not securing adequate supplies, especially of good quality water. T...

  16. Multiple Scattering Effects in EXAFS (Extended X-Ray Absorption Fine Structure): Comparison between Theory and Experiment for Pt Metal.

    Science.gov (United States)

    1984-05-29

    radial distribution and inverse transform of this range. The region commonly used for the inverse transform usually corresponds to the first or second...r-space and comparing it with the corresponding model function. Figure 5 shows the filtered spectra (k weighting), where the pe. 48 allowed inverse ... transform range was successively increased from the radial distance corresponding to the first shell to all the first four shells. There are no multiple

  17. The application of microcatheter superselective catheterization in interventional chemoembolization for multiple hepatocarcinomas: an initial experience in 34 cases

    International Nuclear Information System (INIS)

    Xu Xiaolu; Chen Yongqiang; Wang Qing

    2012-01-01

    Objective: To assess the clinical value of superselective catheterization by using microcatheter in interventional chemoembolization for multiple hepatocarcinomas. Methods: A total of 68 patients with multiple hepatocarcinomas were enrolled in this study. The clinical data were retrospectively analyzed. Superselective catheterization by using a microcatheter was carried out in 34 cases (study group) and superselective catheterization by using a 4-5 F common catheter was performed in 34 cases (control group). The hepatic dysfunctions and the survival rate at 0.5, 1, 2 years were compared between the two groups. Results: The liver function of the patients in study group was much better than that of the patients in control group (P<0.05), and the survival time of the patients in study group was much longer than that of the patients in control group (P<0.05). Conclusion: For the treatment of multiple hepatocarcinomas, interventional chemoembolization by using microcatheter superselective catheterization technique is technically simple and clinically effective with high success rate and fewer complications. (authors)

  18. Multiple production around 1000 TeV observed in the emulsion chamber experiments at Mt. Fuji and linkage experiments with air shower

    International Nuclear Information System (INIS)

    Torii, Syoji

    1980-01-01

    The multiple production around 1000 TeV is discussed in this paper by using the experimental data at Mt. Fuji and the results of the Monte Carlo simulation. Six events with the total energy more than 1000 TeV were observed in the emulsion chamber (EC) exposed for 600 m 2 year at Mt. Fuji. Various Monte Carlo calculations with the scaling model were performed. The relation between the transverse momentum and The Feynman scaling law is discussed. The frequency of the total gamma energy spectrum and the lateral distribution of the family were compared with the calculation. In the case that protons are dominant in primary cosmic ray, the multiplicity in the interaction increased according to 1/4 th power of energy. In the case of heavy nuclei, the experimental results can be reproduced by assuming the increase of cross-section, when the scaling holds. It is still hard to make definite conclusion on the break of scaling. Simultaneous observation of air family and air shower is proposed. (Kato, T.)

  19. Troubled Waters: where Multiple Streams of Inequality Converge in the Math and Science Experiences of Nonprivileged Girls

    Science.gov (United States)

    Parrott, Laurel; Spatig, Linda; Kusimo, Patricia S.; Carter, Carolyn C.; Keyes, Marian

    Water is often hardest to navigate at the confluence of individual streams. As they experience math and science, nonprivileged girls maneuver through roiling waters where the streams of gender, ethnicity, poverty, place, and teaching practices converge. Just as waters of separate streams blend, these issues - too often considered separate factors - become blended and difficult to isolate, and the resulting turbulence produces a bumpy ride. We draw on 3 years of qualitative data collected as part of an intervention program to explore the math and science experiences and perceptions of a group of ethnically diverse, low socioeconomic status rural and urban adolescent Appalachian girls. After describing program and community contexts, we explore "opportunity to leant" issues - specifically, expectations, access to content, and support networks - and examine their schooling experiences against visions of science and math reform and pressures for accountability. Data are discussed within a framework of critical educational theory.

  20. Multiple Parton Interactions in p$bar{p}$ Collisions in D0 Experiment at the Tevatron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Golovanov, Georgy [Joint Inst. for Nuclear Research (JINR), Dubna (Russia)

    2016-01-01

    The thesis is devoted to the study of processes with multiple parton interactions (MPI) in a ppbar collision collected by D0 detector at the Fermilab Tevatron collider at sqrt(s) = 1.96 TeV. The study includes measurements of MPI event fraction and effective cross section, a process-independent parameter related to the effective interaction region inside the nucleon. The measurements are done using events with a photon and three hadronic jets in the final state. The measured effective cross section is used to estimate background from MPI for WH production at the Tevatron energy

  1. Hypoxia in Tumor Angiogenesis and Metastasis: Evaluation of VEGF and MMP Over-expression and Down-Regulation of HIF-1alpha with RNAi in Hypoxic Tumor Cells

    Science.gov (United States)

    Shah, Shruti

    Background: As tumor mass grows beyond a few millimeters in diameter, the angiogenic "switch" is turned on leading to recruitment of blood vessels from surrounding artery and veins. However, the tumor mass is poorly perfused and there are pockets of hypoxia or lower oxygen concentrations relative to normal tissue. Hypoxia-inducing factor-1a (HIF-1a), a transcription factor, is activated when the oxygen concentration is low. Upon activation of HIF-1a, a number of other genes also turn on that allows the tumor to become more aggressive and resistant to therapy. Purpose: The main objectives of this study were to evaluate the effect of hypoxia-induced HIF-1a followed by over-expression of angiogenic and metastatic markers in tumor cells and down-regulation of HIF-1a using nanoparticle-delivered RNA interference therapy. Methods: Human ovarian (SKOV3) and breast (MDA-MB-231) adenocarcinoma cells were incubated under normoxic and hypoxic conditions. Following hypoxia treatment of the cells, HIF-1α, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), and MMP-9 expression was analyzed qualitatively and quantitatively. For intracellular delivery of HIF-1a gene silencing small interfering RNA (siRNA), type B gelatin nanoparticles were fabricated using the solvent displacement method and the surface was modified with poly(ethylene glycol) (PEG, Mol. wt. 2kDa). Cellular uptake and distribution of the nanoparticles was observed with Cy3-siRNA loaded, FITC-conjugated gelatin nanoparticles. Cytotoxicity of the nanoparticle formulations was evaluated in both the cell lines. siRNA was transfected in the gelatin nanoparticles under hypoxic conditions. Total cellular protein and RNA were extracted for analysis of HIF1a, VEGF, MMP-2 and MMP-9 expression. Results: MDA-MB-231 and SKOV3 cells show increased expression of HIF1a under hypoxic conditions compared to baseline levels at normoxic conditions. ELISA and western blots of VEGF, MMP-2 and MMP-9 appear to

  2. Maximizing the sensitivity and reliability of peptide identification in large-scale proteomic experiments by harnessing multiple search engines.

    Science.gov (United States)

    Yu, Wen; Taylor, J Alex; Davis, Michael T; Bonilla, Leo E; Lee, Kimberly A; Auger, Paul L; Farnsworth, Chris C; Welcher, Andrew A; Patterson, Scott D

    2010-03-01

    Despite recent advances in qualitative proteomics, the automatic identification of peptides with optimal sensitivity and accuracy remains a difficult goal. To address this deficiency, a novel algorithm, Multiple Search Engines, Normalization and Consensus is described. The method employs six search engines and a re-scoring engine to search MS/MS spectra against protein and decoy sequences. After the peptide hits from each engine are normalized to error rates estimated from the decoy hits, peptide assignments are then deduced using a minimum consensus model. These assignments are produced in a series of progressively relaxed false-discovery rates, thus enabling a comprehensive interpretation of the data set. Additionally, the estimated false-discovery rate was found to have good concordance with the observed false-positive rate calculated from known identities. Benchmarking against standard proteins data sets (ISBv1, sPRG2006) and their published analysis, demonstrated that the Multiple Search Engines, Normalization and Consensus algorithm consistently achieved significantly higher sensitivity in peptide identifications, which led to increased or more robust protein identifications in all data sets compared with prior methods. The sensitivity and the false-positive rate of peptide identification exhibit an inverse-proportional and linear relationship with the number of participating search engines.

  3. Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats

    International Nuclear Information System (INIS)

    Yin Jinbo; Ma Yuxin; Yin Qing; Xu Haiwei; An Ning; Liu Shiyong; Fan Xiaotang; Yang Hui

    2007-01-01

    The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process and explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after First PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression

  4. Over-expression of a NAC 67 transcription factor from finger millet (Eleusine coracana L.) confers tolerance against salinity and drought stress in rice.

    Science.gov (United States)

    Rahman, Hifzur; Ramanathan, Valarmathi; Nallathambi, Jagedeeshselvam; Duraialagaraja, Sudhakar; Muthurajan, Raveendran

    2016-05-11

    NAC proteins (NAM (No apical meristem), ATAF (Arabidopsis transcription activation factor) and CUC (cup-shaped cotyledon)) are plant-specific transcription factors reported to be involved in regulating growth, development and stress responses. Salinity responsive transcriptome profiling in a set of contrasting finger millet genotypes through RNA-sequencing resulted in the identification of a NAC homolog (EcNAC 67) exhibiting differential salinity responsive expression pattern. Full length cDNA of EcNAC67 was isolated, characterized and validated for its role in abiotic stress tolerance through agrobacterium mediated genetic transformation in a rice cultivar ASD16. Bioinformatics analysis of putative NAC transcription factor (TF) isolated from a salinity tolerant finger millet showed its genetic relatedness to NAC67 family TFs in related cereals. Putative transgenic lines of rice over-expressing EcNAC67 were generated through Agrobacterium mediated transformation and presence/integration of transgene was confirmed through PCR and southern hybridization analysis. Transgenic rice plants harboring EcNAC67 showed enhanced tolerance against drought and salinity under greenhouse conditions. Transgenic rice plants were found to possess higher root and shoot biomass during stress and showed better revival ability upon relief from salinity stress. Upon drought stress, transgenic lines were found to maintain higher relative water content and lesser reduction in grain yield when compared to non-transgenic ASD16 plants. Drought induced spikelet sterility was found to be much lower in the transgenic lines than the non-transgenic ASD16. Results revealed the significant role of EcNAC67 in modulating responses against dehydration stress in rice. No detectable abnormalities in the phenotypic traits were observed in the transgenic plants under normal growth conditions. Results indicate that EcNAC67 can be used as a novel source for engineering tolerance against drought and salinity

  5. AHR over-expression in papillary thyroid carcinoma: clinical and molecular assessments in a series of Italian acromegalic patients with a long-term follow-up.

    Directory of Open Access Journals (Sweden)

    Caterina Mian

    Full Text Available Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3-7%. Germline mutations in the aryl-hydrocarbon receptor (AHR interacting protein (AIP have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer.Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied.12 DTCs (10 papillary and 2 follicular carcinomas were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status.The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma.

  6. TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

    International Nuclear Information System (INIS)

    Schneiderman, Rosa S; Shmueli, Esther; Kirson, Eilon D; Palti, Yoram

    2010-01-01

    Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin. Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt R1 ; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs. TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells. The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors

  7. Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2015-03-01

    Full Text Available Our previous studies in zebrafish development have led to identification of the novel roles of the transient receptor potential melastatin-subfamily member 7 (TRPM7 ion channels in human pancreatic cancer. However, the biological significance of TRPM7 channels in pancreatic neoplasms was mostly unexplored. In this study, we determined the expression levels of TRPM7 in pancreatic tissue microarrays and correlated these measurements in pancreatic adenocarcinoma with the clinicopathological features. We also investigated the role of TRPM7 channels in pancreatic cancer cell invasion using the MatrigelTM-coated transwell assay. In normal pancreas, TRPM7 is expressed at a discernable level in the ductal cells and centroacinar cells and at a relatively high level in the islet endocrine cells. In chronic pancreatitis, pre-malignant tissues, and malignant neoplasms, there is variable expression of TRPM7. In the majority of pancreatic adenocarcinoma specimens examined, TRPM7 is expressed at either moderate-level or high-level. Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors. In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion. The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells. We propose that TRPM7 channels play important roles in development and progression of pancreatic neoplasm, and they may be explored as clinical biomarkers and targets for its prevention and treatment.

  8. Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression.

    Science.gov (United States)

    Escudero-Lourdes, C; Uresti-Rivera, E E; Oliva-González, C; Torres-Ramos, M A; Aguirre-Bañuelos, P; Gandolfi, A J

    2016-10-01

    Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA III ), which accumulates in glial cells without compromising cell viability. MMA III LD 50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA III concentrations (50-1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA III concentrations that also induced TNF-α over-expression. Other effects of MMA III on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA III concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA III induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

  9. Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles

    International Nuclear Information System (INIS)

    Lin, C.-L.; Leu, Steve; Lu, M.-C.; Ouyang Pin

    2004-01-01

    Pre-mRNA splicing takes place within a dynamic ribonucleoprotein particle called the spliceosome and occurs in an ordered pathway. Although it is known that spliceosome consists of five small nuclear RNAs and at least 50 proteins, little is known about how the interaction among the proteins changes during splicing. Here we identify that SR-cyp, a Moca family of nuclear cyclophilin, interacts and colocalizes with nuclear pinin (pnn), a SR-related protein involving in pre-mRNA splicing. Nuclear pnn interacts with SR-cyp via its C-terminal RS domain. Upon SR-cyp over-expression, however, the subnuclear distribution of nuclear pnn is altered, resulting in its redistribution from nuclear speckles to a diffuse nucleoplasmic form. The diffuse subnuclear distribution of nuclear pnn is not due to epitope masking, accelerated protein turnover or post-translational modification. Furthermore, we find that SR-cyp regulates the subnuclear distribution of other SR family proteins, including SC35 and SRm300, in a similar manner as it does on nuclear pnn. This result is significant because it suggests that SR-cyp plays a general role in modulating the distribution pattern of SR-like and SR proteins, similar to that of Clk (cdc2-like kinase)/STY on SR family splicing factors. SR-cyp might direct its effect via either alteration of protein folding/conformation or of protein-protein interaction and thus may add another control level of regulation of SR family proteins and modification of their functions

  10. Overview of the Bushland Evapotranspiration and Agricultural Remote sensing EXperiment 2008 (BEAREX08): A field experiment evaluating methods for quantifying ET at multiple scales

    Science.gov (United States)

    Evett, Steven R.; Kustas, William P.; Gowda, Prasanna H.; Anderson, Martha C.; Prueger, John H.; Howell, Terry A.

    2012-12-01

    In 2008, scientists from seven federal and state institutions worked together to investigate temporal and spatial variations of evapotranspiration (ET) and surface energy balance in a semi-arid irrigated and dryland agricultural region of the Southern High Plains in the Texas Panhandle. This Bushland Evapotranspiration and Agricultural Remote sensing EXperiment 2008 (BEAREX08) involved determination of micrometeorological fluxes (surface energy balance) in four weighing lysimeter fields (each 4.7 ha) containing irrigated and dryland cotton and in nearby bare soil, wheat stubble and rangeland fields using nine eddy covariance stations, three large aperture scintillometers, and three Bowen ratio systems. In coordination with satellite overpasses, flux and remote sensing aircraft flew transects over the surrounding fields and region encompassing an area contributing fluxes from 10 to 30 km upwind of the USDA-ARS lysimeter site. Tethered balloon soundings were conducted over the irrigated fields to investigate the effect of advection on local boundary layer development. Local ET was measured using four large weighing lysimeters, while field scale estimates were made by soil water balance with a network of neutron probe profile water sites and from the stationary flux systems. Aircraft and satellite imagery were obtained at different spatial and temporal resolutions. Plot-scale experiments dealt with row orientation and crop height effects on spatial and temporal patterns of soil surface temperature, soil water content, soil heat flux, evaporation from soil in the interrow, plant transpiration and canopy and soil radiation fluxes. The BEAREX08 field experiment was unique in its assessment of ET fluxes over a broad range in spatial scales; comparing direct and indirect methods at local scales with remote sensing based methods and models using aircraft and satellite imagery at local to regional scales, and comparing mass balance-based ET ground truth with eddy covariance

  11. The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Yara Dadalti Fragoso

    2014-09-01

    Full Text Available Fingolimod is a new and efficient treatment for multiple sclerosis (MS. The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

  12. [Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis].

    Science.gov (United States)

    Rossiev, V A; Makarov, S V; Aleksandrova, I Ia; Dolgikh, G T; Lipshina, S R; Stukalova, T A; Trushina, O A; Fedorova, E Iu; Lipina, L N; Sivak, V F; Korenev, P P; Murashov, B F

    2002-01-01

    To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

  13. Development and performance test of a system available for generating multiple extreme conditions for neutron scattering experiments

    International Nuclear Information System (INIS)

    Kawano, Shinji; Fukui, Susumu; Moriai, Atsushi; Ohtomo, Akitoshi; Ichimura, Shigeki; Onodera, Akifumi; Amita, F.; Katano, Susumu

    1998-01-01

    We have developed unique system available for controlling sample environment during the neutron scattering experiments. The system can simultaneously generate triple extreme conditions of low temperature, high magnetic field and high pressure. The system consists of: (i) a liquid-helium cryostat variable for sample temperature from 1.7 K to 200 K, (ii) a superconducting magnet providing a vertical field up to ±5 T with an antisymmetric split-coil geometry for polarized-beam experiments, and (iii) a non-magnetic piston-cylinder high-pressure cell designed with the aim of generating hydrostatic pressure up to 2.5 GPa. In the presentation, we will report the outline of the system and some results of performance tests at KURRI and JRR-3M of JAERI. (author)

  14. Measuring decision weights in recognition experiments with multiple response alternatives: comparing the correlation and multinomial-logistic-regression methods.

    Science.gov (United States)

    Dai, Huanping; Micheyl, Christophe

    2012-11-01

    Psychophysical "reverse-correlation" methods allow researchers to gain insight into the perceptual representations and decision weighting strategies of individual subjects in perceptual tasks. Although these methods have gained momentum, until recently their development was limited to experiments involving only two response categories. Recently, two approaches for estimating decision weights in m-alternative experiments have been put forward. One approach extends the two-category correlation method to m > 2 alternatives; the second uses multinomial logistic regression (MLR). In this article, the relative merits of the two methods are discussed, and the issues of convergence and statistical efficiency of the methods are evaluated quantitatively using Monte Carlo simulations. The results indicate that, for a range of values of the number of trials, the estimated weighting patterns are closer to their asymptotic values for the correlation method than for the MLR method. Moreover, for the MLR method, weight estimates for different stimulus components can exhibit strong correlations, making the analysis and interpretation of measured weighting patterns less straightforward than for the correlation method. These and other advantages of the correlation method, which include computational simplicity and a close relationship to other well-established psychophysical reverse-correlation methods, make it an attractive tool to uncover decision strategies in m-alternative experiments.

  15. 16-channel analyser with high time-resolution for multiple coincidence experiments; Selecteur a 16 canaux a temps de resolution eleve pour experiences de coincidences multiples; Ispol'zovanie shestiadtsatikanal'nogo analizatora s bol'shoj razreshayushchej sposobnost'yu po vremeni dlya opytov s mnogokratnymi sovpadeniyami; Analizador de 16 canales de elevado poder temporal de resolucion para experimentos de coincidencias multiples

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B; Cappeller, U [University of Marburg, Marburg, Federal Republic of Germany (Germany)

    1962-04-15

    In usual slow-fast-coincidence experiments such events are counted which are selected in pulse-height by means of single-channel analysers. It is desirable to extend these techniques to a simultaneous energy-analysis of the pulses, selecting pulse-heights by means of multi-channel analysers. Multi-channel analysers used to perform such multiple coincidence experiments should give information about the amplitudes of arriving pulses at a well defined time-interval after the rising of the analysed pulse. A 16-channel pulse-height analyser is described which permits the generation of a pulse-height signal 2.5 x 10{sup -6} s after pulse-rising with an uncertainty of less than {+-} 2 x 10{sup -8} s. The resolving-time is less than 5 x 10{sup -6} s, controlled by an inspector-circuit to avoid distortions arising from the pile-up of pulses. The channel width is controlled by a window-amplifier, adjustable from 1 V to 7 V. The channel-height may be selected from 7 V to 103 V in steps of 0.5 V. (author) [French] En general, dans les experiences de coincidences lentes-rapides, on compte des evenements traduits sous forme d'impulsions dont l'amplitude est selectionnee a l'aide de selecteurs a un seul canal. Il est souhaitable d'etendre cette technique a l'analyse simultanee de l'energie des impulsions, en selectionnant les amplitudes au moyen de selecteurs a canaux multiples. Les selecteurs multi-canaux utilises pour ces experiences de coincidences multiples devraient fournir une indication sur les amplitudes des impulsions d'entree a un intervalle de temps bien defini, apres la montee de l'impulsion analysee. Les auteurs decrivent un selecteur d'amplitude a 16 canaux, qui delivre un signal 2,5 {center_dot} 10{sup -6} s apres l'etablissement de l'impulsion avec une erreur inferieure a {+-} 2 {center_dot} 10{sup -8} s. Le temps de resolution, inferieur a 5 {center_dot} 10{sup -6} s, est commande par un circuit special pour eviter les derangements qui resulteraient de l

  16. Lesion type and reader experience affect the diagnostic accuracy of breast MRI: A multiple reader ROC study

    Energy Technology Data Exchange (ETDEWEB)

    Baltzer, Pascal A.T., E-mail: patbaltzer@gmail.com [Department of Biomedical Imaging and Imge-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna (Austria); Kaiser, Werner Alois [Department of Diagnostic and Interventional Radiology, University Hospital Jena, Erlanger Allee 101, 07740 Jena (Germany); Dietzel, Matthias, E-mail: dietzelmatthias2@hotmail.com [Department of Neuroradiology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen (Germany)

    2015-01-15

    Highlights: • The main findings of our study are, that reader experience and lesion type (i.e., mass versus non-mass enhancement) are independent predictors of the diagnostic accuracy of breast MRI. • Specifically, benign and malignant non-mass lesions cannot be differentiated with sufficient accuracy, especially if readers are not experienced. • We conclude that future research in breast MRI should focus on non-mass lesions, as these are the problem makers in modern breast MRI. - Abstract: Purpose: To evaluate the influence of lesion type (mass versus non-mass) and reader experience on the diagnostic performance of breast MRI (BMRI) in a non-screening setting. Materials and methods: Consecutive patients (mean age, 55 ± 12 years) with breast lesions that were verified by biopsy or surgery, and who had had BMRI as part of their diagnostic workup, were eligible for this retrospective single-center study. Cancers diagnosed by biopsy before BMRI were excluded to eliminate biological and interpretation bias due to biopsy or chemotherapy effects (n = 103). Six blinded readers (experience level, high (HE, n = 2); intermediate (IE, n = 2); and low (LE, n = 2)) evaluated all examinations and assigned independent MRI BI-RADS ratings. Lesion type (mass, non-mass, focal) was noted. Receiver operating characteristics (ROC) and logistic regression analysis was performed to compare diagnostic accuracies. Results: There were 259 histologically verified lesions (123 malignant, 136 benign) investigated. There were 169 mass (103 malignant, 66 benign) and 48 non-mass lesions (19 malignant, 29 benign). Another 42 lesions that met the inclusion criteria were biopsied due to conventional findings (i.e., microcalcifications, architectural distortions), but did not enhance on MRI (41 benign, one DCIS). ROC analysis revealed a total area under the curve (AUC) between 0.834 (LE) and 0.935 (HI). Logistic regression identified a significant effect of non-mass lesions (P < 0.0001) and

  17. Comprehensive ecosystem model-experiment synthesis using multiple datasets at two temperate forest free-air CO2 enrichment experiments: model performance and compensating biases

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Anthony P [ORNL; Hanson, Paul J [ORNL; DeKauwe, Martin G [Macquarie University; Medlyn, Belinda [Macquarie University; Zaehle, S [Max Planck Institute for Biogeochemistry; Asao, Shinichi [Colorado State University, Fort Collins; Dietze, Michael [University of Illinois, Urbana-Champaign; Hickler, Thomas [Goethe University, Frankfurt, Germany; Huntinford, Chris [Centre for Ecology and Hydrology, Wallingford, United Kingdom; Iversen, Colleen M [ORNL; Jain, Atul [University of Illinois, Urbana-Champaign; Lomas, Mark [University of Sheffield; Luo, Yiqi [University of Oklahoma; McCarthy, Heather R [Duke University; Parton, William [Colorado State University, Fort Collins; Prentice, I. Collin [Macquarie University; Thornton, Peter E [ORNL; Wang, Shusen [Canada Centre for Remote Sensing (CCRS); Wang, Yingping [CSIRO Marine and Atmospheric Research; Warlind, David [Lund University, Sweden; Weng, Ensheng [University of Oklahoma, Norman; Warren, Jeffrey [ORNL; Woodward, F. Ian [University of Sheffield; Oren, Ram [Duke University; Norby, Richard J [ORNL

    2014-01-01

    Free Air CO2 Enrichment (FACE) experiments provide a remarkable wealth of data to test the sensitivities of terrestrial ecosystem models (TEMs). In this study, a broad set of 11 TEMs were compared to 22 years of data from two contrasting FACE experiments in temperate forests of the south eastern US the evergreen Duke Forest and the deciduous Oak Ridge forest. We evaluated the models' ability to reproduce observed net primary productivity (NPP), transpiration and Leaf Area index (LAI) in ambient CO2 treatments. Encouragingly, many models simulated annual NPP and transpiration within observed uncertainty. Daily transpiration model errors were often related to errors in leaf area phenology and peak LAI. Our analysis demonstrates that the simulation of LAI often drives the simulation of transpiration and hence there is a need to adopt the most appropriate of hypothesis driven methods to simulate and predict LAI. Of the three competing hypotheses determining peak LAI (1) optimisation to maximise carbon export, (2) increasing SLA with canopy depth and (3) the pipe model the pipe model produced LAI closest to the observations. Modelled phenology was either prescribed or based on broader empirical calibrations to climate. In some cases, simulation accuracy was achieved through compensating biases in component variables. For example, NPP accuracy was sometimes achieved with counter-balancing biases in nitrogen use efficiency and nitrogen uptake. Combined analysis of parallel measurements aides the identification of offsetting biases; without which over-confidence in model abilities to predict ecosystem function may emerge, potentially leading to erroneous predictions of change under future climates.

  18. Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States

    Directory of Open Access Journals (Sweden)

    Jara M

    2015-12-01

    Full Text Available Michele Jara, Thomas Aquilina, Peter Aupperle, Adrian L Rabinowicz Acorda Therapeutics, Inc., Ardsley, NY, USA Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US, 10 mg twice daily, was approved by the US Food and Drug Administration (FDA in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. Objective: To provide a descriptive analysis of reported adverse events (AEs for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Methods: Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years. Commonly reported AEs (≥2% of all reported AEs and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Results: Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1, the most common AEs were dizziness (3.7%, insomnia (3.2%, balance disorder (3%, fall (2.4%, headache (2.4%, nausea (2.1%, and urinary tract infection (2%. Other common AEs were drug ineffectiveness (5.8%, gait disturbance (4.6%, and inappropriate dosing (3.1%. Serious AEs included rare anaphylactic reactions (five cases and drug hypersensitivity reactions (eight cases. A total of 657 seizure cases were reported (6.3/1,000 patient-years; of these, 324 were medically confirmed (3.1/1,000 patient-years. Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to >4 years; 12% of the seizures occurred within a week of starting treatment. Conclusion: The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a

  19. First experience with multiple mini interview for medical school admission in Brazil: Does it work in a different cultural scenario?

    Science.gov (United States)

    Daniel-Filho, Durval Anibal; Pires, Elda Maria Stafuzza Gonçalves; Paes, Angela Tavares; Troster, Eduardo Juan; Silva, Simone Cristina Azevedo B S; Granato, Mariana Fachini; Couto, Thomaz Bittencourt; Barreto, Joyce Kelly Silva; Campos, Alexandre Holthausen; Monte, Julio C Martins; Schvartsman, Claudio

    2017-10-01

    Evaluation of non-cognitive skills never has been used in Brazil. This study aims to evaluate Multiple Mini Interviews (MMI) in the admission process of a School of Medicine in São Paulo, Brazil. The population of the study comprised 240 applicants summoned for the interviews, and 96 raters. MMI contributed to 25% of the applicants' final grade. Eight scenarios were created with the aim of evaluating different non-cognitive skills, each one had two raters. At the end of the interviews, the applicants and raters described their impressions about MMI. The reliability of the MMI was analyzed using the Theory of Generalization and Many-Facet Rasch Model (MFRM). The G-study showed that the general reliability of the process was satisfactory (coefficient G = 0.743). The MMI grades were not affected by the raters' profile, time of interview (p = 0.715), and randomization group (p = 0.353). The Rasch analysis showed that there was no misfitting effects or inconsistent stations or raters. A significant majority of the applicants (98%) and all the raters believed MMIs were important in selecting students with a more adequate profile to study medicine. The general reliability of the selection process was excellent, and it was fully accepted by the applicants and raters.

  20. Student ownership of projects in an upper-division optics laboratory course: A multiple case study of successful experiences

    Directory of Open Access Journals (Sweden)

    Dimitri R. Dounas-Frazer

    2017-12-01

    Full Text Available We investigate students’ sense of ownership of multiweek final projects in an upper-division optics lab course. Using a multiple case study approach, we describe three student projects in detail. Within-case analyses focused on identifying key issues in each project, and constructing chronological descriptions of those events. Cross-case analysis focused on identifying emergent themes with respect to five dimensions of project ownership: student agency, instructor mentorship, peer collaboration, interest and value, and affective responses. Our within- and cross-case analyses yielded three major findings. First, coupling division of labor with collective brainstorming can help balance student agency, instructor mentorship, and peer collaboration. Second, students’ interest in the project and perceptions of its value can increase over time; initial student interest in the project topic is not a necessary condition for student ownership of the project. Third, student ownership is characterized by a wide range of emotions that fluctuate as students alternate between extended periods of struggle and moments of success while working on their projects. These findings not only extend the literature on student ownership into a new educational domain—namely, upper-division physics labs—they also have concrete implications for the design of experimental physics projects in courses for which student ownership is a desired learning outcome. We describe the course and projects in sufficient detail that others can adapt our results to their particular contexts.

  1. Theory and simulations of covariance mapping in multiple dimensions for data analysis in high-event-rate experiments

    Science.gov (United States)

    Zhaunerchyk, V.; Frasinski, L. J.; Eland, J. H. D.; Feifel, R.

    2014-05-01

    Multidimensional covariance analysis and its validity for correlation of processes leading to multiple products are investigated from a theoretical point of view. The need to correct for false correlations induced by experimental parameters which fluctuate from shot to shot, such as the intensity of self-amplified spontaneous emission x-ray free-electron laser pulses, is emphasized. Threefold covariance analysis based on simple extension of the two-variable formulation is shown to be valid for variables exhibiting Poisson statistics. In this case, false correlations arising from fluctuations in an unstable experimental parameter that scale linearly with signals can be eliminated by threefold partial covariance analysis, as defined here. Fourfold covariance based on the same simple extension is found to be invalid in general. Where fluctuations in an unstable parameter induce nonlinear signal variations, a technique of contingent covariance analysis is proposed here to suppress false correlations. In this paper we also show a method to eliminate false correlations associated with fluctuations of several unstable experimental parameters.

  2. Student ownership of projects in an upper-division optics laboratory course: A multiple case study of successful experiences

    Science.gov (United States)

    Dounas-Frazer, Dimitri R.; Stanley, Jacob T.; Lewandowski, H. J.

    2017-12-01

    We investigate students' sense of ownership of multiweek final projects in an upper-division optics lab course. Using a multiple case study approach, we describe three student projects in detail. Within-case analyses focused on identifying key issues in each project, and constructing chronological descriptions of those events. Cross-case analysis focused on identifying emergent themes with respect to five dimensions of project ownership: student agency, instructor mentorship, peer collaboration, interest and value, and affective responses. Our within- and cross-case analyses yielded three major findings. First, coupling division of labor with collective brainstorming can help balance student agency, instructor mentorship, and peer collaboration. Second, students' interest in the project and perceptions of its value can increase over time; initial student interest in the project topic is not a necessary condition for student ownership of the project. Third, student ownership is characterized by a wide range of emotions that fluctuate as students alternate between extended periods of struggle and moments of success while working on their projects. These findings not only extend the literature on student ownership into a new educational domain—namely, upper-division physics labs—they also have concrete implications for the design of experimental physics projects in courses for which student ownership is a desired learning outcome. We describe the course and projects in sufficient detail that others can adapt our results to their particular contexts.

  3. Prognostic factors and outcome in relapsed multiple myeloma after nonmyeloablative allo-SCT: a single center experience.

    Science.gov (United States)

    Minnema, M C; van Dorp, S; van de Donk, N W C J; Schouten, F; Kersten, M J; Coenen, J L L M; Schouten, H; Zweegman, S; Schaafsma, R; Lokhorst, H M

    2011-02-01

    For relapsed multiple myeloma (MM) patients, allo-SCT is a possible treatment option, but recent data obtained using a nonmyeloablative (NMA) conditioning regimen are scarce. We retrospectively collected data from 38 relapsed MM patients who received a NMA allo-SCT from October 2001 to January 2008. In total, 18 patients (48%) were transplanted using a matched unrelated donor. The median follow-up is 2.3 years. In 16 patients (42%) the response improved and eight patients (21%) were rapidly progressive within 6 months after allo-SCT. In total, 15 patients (39%) were in CR after allo-SCT. The median PFS was 1.4 years (range, 0.1-4.9), and having a CR after allo-SCT or having chronic GVHD resulted in longer PFS. Median OS was 3.1 years (range, 0.2-7.2) and again having a CR after allo-SCT or chronic GVHD was associated with a better OS. Six patients (16%) have died from treatment-related diseases. These results indicate that NMA allo-SCT is a treatment option in relapsed MM patients and that results may be improved by strategies that enhance the CR rate after allo-SCT.

  4. Formation of multiple stoichiometric phases in binary systems by combined bulk and grain boundary diffusion: Experiments and model

    International Nuclear Information System (INIS)

    Svoboda, J.; Fischer, F.D.; Schillinger, W.

    2013-01-01

    The thermodynamic extremal principle has been used by the authors to treat the evolution of binary and multicomponent systems under the assumption that all phases are nearly stoichiometric. Up to now only bulk diffusion has been taken into account. The concept is now extended to combined bulk and grain boundary diffusion possible in each newly formed phase. The grains are approximated by cylinders allowing interface diffusion along the top and bottom of the grains and grain boundary diffusion along the mantle with different interface/grain boundary diffusion coefficients. A consistent analysis yields an effective diffusion coefficient taking into account the combined interface/grain boundary and bulk diffusion of each individual component. The current concept is applied to the Cu–Sn couple which has been studied by a number of researchers. The results of simulations are compared with experiments at 200 °C on solid systems reported in the literature as well as with our experiments at 250 °C with liquid Sn.

  5. Genome-Wide Screening of Cytogenetic Abnormalities in Multiple Myeloma Patients Using Array-CGH Technique: A Czech Multicenter Experience

    Directory of Open Access Journals (Sweden)

    Jan Smetana

    2014-01-01

    Full Text Available Characteristic recurrent copy number aberrations (CNAs play a key role in multiple myeloma (MM pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH provides a powerful tool for genome-wide classification of CNAs and thus should be implemented into MM routine diagnostics. We demonstrate the possibility of effective utilization of oligonucleotide-based aCGH in 91 MM patients. Chromosomal aberrations associated with effect on the prognosis of MM were initially evaluated by I-FISH and were found in 93.4% (85/91. Incidence of hyperdiploidy was 49.5% (45/91; del(13(q14 was detected in 57.1% (52/91; gain(1(q21 occurred in 58.2% (53/91; del(17(p13 was observed in 15.4% (14/91; and t(4;14(p16;q32 was found in 18.6% (16/86. Genome-wide screening using Agilent 44K aCGH microarrays revealed copy number alterations in 100% (91/91. Most common deletions were found at 13q (58.9%, 1p (39.6%, and 8p (31.1%, whereas gain of whole 1q was the most often duplicated region (50.6%. Furthermore, frequent homozygous deletions of genes playing important role in myeloma biology such as TRAF3, BIRC1/BIRC2, RB1, or CDKN2C were observed. Taken together, we demonstrated the utilization of aCGH technique in clinical diagnostics as powerful tool for identification of unbalanced genomic abnormalities with prognostic significance for MM patients.

  6. Reducing the standard deviation in multiple-assay experiments where the variation matters but the absolute value does not.

    Science.gov (United States)

    Echenique-Robba, Pablo; Nelo-Bazán, María Alejandra; Carrodeguas, José A

    2013-01-01

    When the value of a quantity x for a number of systems (cells, molecules, people, chunks of metal, DNA vectors, so on) is measured and the aim is to replicate the whole set again for different trials or assays, despite the efforts for a near-equal design, scientists might often obtain quite different measurements. As a consequence, some systems' averages present standard deviations that are too large to render statistically significant results. This work presents a novel correction method of a very low mathematical and numerical complexity that can reduce the standard deviation of such results and increase their statistical significance. Two conditions are to be met: the inter-system variations of x matter while its absolute value does not, and a similar tendency in the values of x must be present in the different assays (or in other words, the results corresponding to different assays must present a high linear correlation). We demonstrate the improvements this method offers with a cell biology experiment, but it can definitely be applied to any problem that conforms to the described structure and requirements and in any quantitative scientific field that deals with data subject to uncertainty.

  7. Extracting the Beat: An Experience-dependent Complex Integration of Multisensory Information Involving Multiple Levels of the Nervous System

    Directory of Open Access Journals (Sweden)

    Laurel J. Trainor

    2009-04-01

    Full Text Available In a series of studies we have shown that movement (or vestibular stimulation that is synchronized to every second or every third beat of a metrically ambiguous rhythm pattern biases people to perceive the meter as a march or as a waltz, respectively. Riggle (this volume claims that we postulate an "innate", "specialized brain unit" for beat perception that is "directly" influenced by vestibular input. In fact, to the contrary, we argue that experience likely plays a large role in the development of rhythmic auditory-movement interactions, and that rhythmic processing in the brain is widely distributed and includes subcortical and cortical areas involved in sound processing and movement. Further, we argue that vestibular and auditory information are integrated at various subcortical and cortical levels along with input from other sensory modalities, and it is not clear which levels are most important for rhythm processing or, indeed, what a "direct" influence of vestibular input would mean. Finally, we argue that vestibular input to sound location mechanisms may be involved, but likely cannot explain the influence of vestibular input on the perception of auditory rhythm. This remains an empirical question for future research.

  8. Functional analyses of AtCHR12 and AtCHR23 : plant growth responses upon over-expression of chromatin remodeling ATPase genes

    NARCIS (Netherlands)

    Folta, A.

    2015-01-01

    Living organisms have to deal with changing environmental conditions during their whole life cycle. In contrast to animals, plants are sessile organisms. Therefore they have evolved multiple regulatory mechanisms that help them to cope with changing conditions. One of the first responses to

  9. Multiplicity dependence of two-particle correlation in $\\sqrt{s}$ = 7 TeV pp collisions at LHC-ALICE experiment

    CERN Document Server

    Bhom, Jihyun; Esumi, Shinlchi

    Early stage of universe or inside of neutron stars are supposed to be Quark Gluon Plasma (QGP) state. The QGP is a state of matter in quantum chromodynamics (QCD), which exists at extremely high temperature and/or high density. In high energy nuclear collisions experiment, hot dense matter or QGP has been studied, the collective flow of the system has been one of key issues to understand the state of matter. Large Hadron Collider (LHC) has served pp collisions at a nucleon–nucleon center-of-mass energy of 7 TeV in 2010, where the maximum charged particle multiplicity has been measured as large as 100$\\sim$200 charged particles in $|\\eta|<$2.5 in $dN/d\\eta$ like Cu-Cu collisions $\\sqrt {s_{NN}} = 200$ GeV at mid-peripheral at RHIC. A Large Ion Collider Experiment (ALICE) detector at the LHC is optimized for studying the high-temperature and high-density system called as QGP. Angular correlations between two charged particles are measured with central and forward detectors in ALICE experiment. Th...

  10. Effects of multiple scatter on the propagation and absorption of electromagnetic waves in a field-aligned-striated cold magneto-plasma: implications for ionospheric modification experiments

    Directory of Open Access Journals (Sweden)

    T. R. Robinson

    Full Text Available A new theory of the propagation of low power electromagnetic test waves through the upper-hybrid resonance layer in the presence of magnetic field-aligned plasma density striations, which includes the effects of multiple scatter, is presented. The case of sinusoidal striations in a cold magnetoplasma is treated rigorously and then extended, in an approximate manner, to the broad-band striation spectrum and warm plasma cases. In contrast to previous, single scatter theories, it is found that the interaction layer is much broader than the wavelength of the test wave. This is due to the combined electric fields of the scattered waves becoming localised on the contour of a fixed plasma density, which corresponds to a constant value for the local upper-hybrid resonance frequency over the whole interaction region. The results are applied to the calculation of the refractive index of an ordinary mode test wave during modification experiments in the ionospheric F-region. Although strong anomalous absorption arises, no new cutoffs occur at the upper-hybrid resonance, so that in contrast to the predictions of previous single scatter theories, no additional reflections occur there. These results are consistent with observations made during ionospheric modification experiments at Tromsø, Norway.

    Key words. Ionosphere (active experiments; ionospheric irregularities Radio science (ionospheric propagation

  11. Triple-orifice valve repair in severe Barlow disease with multiple-jet mitral regurgitation: report of mid-term experience.

    Science.gov (United States)

    Fucci, Carlo; Faggiano, Pompilio; Nardi, Matilde; D'Aloia, Antonio; Coletti, Giuseppe; De Cicco, Giuseppe; Latini, Leonardo; Vizzardi, Enrico; Lorusso, Roberto

    2013-09-10

    Barlow disease represents a surgical challenge for mitral valve repair (MR) in the presence of mitral insufficiency (MI) with multiple regurgitant jets. We hereby present our mid-term experience using a modified edge-to-edge technique to address this peculiar MI. From March 2003 till December 2010, 25 consecutive patients (mean age 54 ± 7 years, 14 males) affected by severe Barlow disease with multiple regurgitant jets were submitted to MR. Preoperative transesophageal echo (TEE) in all the cases showed at least 2 regurgitant jets, involving one or both leaflets in more than one segment. In all the patients, a triple orifice valve (TOV) repair with annuloplasty was performed. Intra-operative TEE and postoperative transthoracic echocardiography (TTE) were carried out to evaluate results of the TOV repair. There was no in-hospital death and one late death (non-cardiac related). At intra-operative TEE, the three orifices showed a mean total valve area of 2.9 ± 0.1cm(2) (range 2.5-3.3 cm(2)) with no residual regurgitation (2 cases of trivial MI) and no sign of valve stenosis (mean transvalvular gradient 4.6 ± 1.5 mmHg). At follow up (mean 38 ± 22 months), TTE showed favourable MR and no recurrence of significant MI (6 cases of trivial and 1 of mild MI). Stress TTE was performed in 5 cases showing persistent effective valve function (2 cases of trivial MI at peak exercise). All the patients showed significant NYHA functional class improvement. This report indicates that the TOV technique is effective in correcting complex Barlow mitral valves with multiple jets. Further studies are required to confirm long-term applicability and durability in more numerous clinical cases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Statistical experiments using the multiple regression research for prediction of proper hardness in areas of phosphorus cast-iron brake shoes manufacturing

    Science.gov (United States)

    Kiss, I.; Cioată, V. G.; Ratiu, S. A.; Rackov, M.; Penčić, M.

    2018-01-01

    Multivariate research is important in areas of cast-iron brake shoes manufacturing, because many variables interact with each other simultaneously. This article focuses on expressing the multiple linear regression model related to the hardness assurance by the chemical composition of the phosphorous cast irons destined to the brake shoes, having in view that the regression coefficients will illustrate the unrelated contributions of each independent variable towards predicting the dependent variable. In order to settle the multiple correlations between the hardness of the cast-iron brake shoes, and their chemical compositions several regression equations has been proposed. Is searched a mathematical solution which can determine the optimum chemical composition for the hardness desirable values. Starting from the above-mentioned affirmations two new statistical experiments are effectuated related to the values of Phosphorus [P], Manganese [Mn] and Silicon [Si]. Therefore, the regression equations, which describe the mathematical dependency between the above-mentioned elements and the hardness, are determined. As result, several correlation charts will be revealed.

  13. A multiple choice testing program coupled with a year-long elective experience is associated with improved performance on the internal medicine in-training examination.

    Science.gov (United States)

    Mathis, Bradley R; Warm, Eric J; Schauer, Daniel P; Holmboe, Eric; Rouan, Gregory W

    2011-11-01

    The Internal Medicine In-Training Exam (IM-ITE) assesses the content knowledge of internal medicine trainees. Many programs use the IM-ITE to counsel residents, to create individual remediation plans, and to make fundamental programmatic and curricular modifications. To assess the association between a multiple-choice testing program administered during 12 consecutive months of ambulatory and inpatient elective experience and IM-ITE percentile scores in third post-graduate year (PGY-3) categorical residents. Retrospective cohort study. One hundred and four categorical internal medicine residents. Forty-five residents in the 2008 and 2009 classes participated in the study group, and the 59 residents in the three classes that preceded the use of the testing program, 2005-2007, served as controls. A comprehensive, elective rotation specific, multiple-choice testing program and a separate board review program, both administered during a continuous long-block elective experience during the twelve months between the second post-graduate year (PGY-2) and PGY-3 in-training examinations. We analyzed the change in median individual percent correct and percentile scores between the PGY-1 and PGY-2 IM-ITE and between the PGY-2 and PGY-3 IM-ITE in both control and study cohorts. For our main outcome measure, we compared the change in median individual percentile rank between the control and study cohorts between the PGY-2 and the PGY-3 IM-ITE testing opportunities. After experiencing the educational intervention, the study group demonstrated a significant increase in median individual IM-ITE percentile score between PGY-2 and PGY-3 examinations of 8.5 percentile points (p ITE performance.

  14. Development of Multiple Antibiotic Resistance in Bacillus subtilis Cells Exposed to Microgravity: the BRIC-18 Experiment to the International Space Station

    Science.gov (United States)

    Fajardo-Cavazos, Patricia; Moeller, Ralf; Nicholson, Wayne; Narvel, Raed

    Increased pathogenicity of opportunistic bacteria during long-term spaceflight is considered an astronaut risk. Because only a limited pharmacy can be carried on long-duration missions, the development of resistance to multiple antibiotics is a concern for mission planning. In support of the BRIC-18 experiment to the ISS, we have performed ground-based experiments to address the question whether simulated microgravity affects the frequency of resistance to the model antibiotics rifampicin (RFM) and trimethoprim (TMP). In these experiments, the model bacteria Bacillus subtilis and Staphylococcus epidermidis were cultivated for 6 days at ISS ambient temperature in 10-ml High Aspect Ratio Vessels (HARVs) on two 4-place clinostats (Synthecon) oriented either vertically (V) or horizontally (H). Cells were harvested, enumerated and plated onto medium containing RFM (5 micrograms/ml). The frequency of mutation to RFM resistance was calculated, and RFM-resistant mutants were plated onto medium containing the second antibiotic, TMP (5 micrograms/ml) to determine the frequency of mutation to double (RFM+TMP) resistance. After 6 days of cultivation, V-cultures showed higher cell densities and than H-cultures for both bacteria. However, only in B. subtilis did V-cultures show higher frequencies of mutation to RFM resistance than H-cultures. Launch of BRIC-18 to the ISS is currently scheduled for March 16, 2014 and return 30 days later. Results from both the spaceflight and ground control experiments will be presented. Supported by NASA-SAIP fellowship to R.N. and NASA grant (NNX12AN70G) to P.F.-C., R.M., and W.L.N.

  15. Search for long-lived supersymmetry particles by signature of a high track-multiplicity displaced vertex using the LHC-ATLAS Experiment

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00360876

    Long-lived supersymmetry (SUSY) particles decaying within the tracking volume of the LHC-ATLAS Experiment can be reconstructed as a displaced vertex (DV). The search strategy involves attempting to reassemble the decay point of the long-lived particles (LLPs) by fitting vertices from the trajectories arising from the charged decay products. A search, looking for a signature of a massive high track-multiplicity DV has been conducted using data collected during 2012 by the LHC-ATLAS Experiment at $\\sqrt{s}~=~8$ TeV, equaling to an integrated luminosity of 20.3 fb$^{-1}$. A signature of a massive displaced vertex is especially powerful due to the lack of any heavy long-lived standard model particles. Thereby, giving an analysis that is nearly background free. This dissertation describes the new, much more generic, "$DV+\\text{jets}$" channel. In this channel events with high momentum jets and at least one displaced vertex are considered. Eliminating the requirement of an associated $\\mu$ generated, to date of w...

  16. Qualitative Investigation of Exercise Perceptions and Experiences in People With Multiple Sclerosis Before, During, and After Participation in a Personally Tailored Exercise Program.

    Science.gov (United States)

    Crank, Helen; Carter, Anouska; Humphreys, Liam; Snowdon, Nicky; Daley, Amanda; Woodroofe, Nicola; Sharrack, Basil; Petty, Jane; Saxton, John M

    2017-12-01

    To undertake a qualitative investigation of exercise perceptions and experiences in people with multiple sclerosis (PwMS) before, during, and after participation in a personally tailored program designed to promote long-term maintenance of self-directed exercise. Focus groups and semistructured telephone interviews. University exercise science department close to the recruiting hospital. PwMS (N=33; mean age ± SD, 47.6±7.9y). Participants were recruited after participation in a randomized controlled exercise trial; all had been allocated to a 12-week exercise program comprising supervised and self-directed exercise sessions. Exercise perceptions and experiences before, during, and after participation in the program. Four themes emerged from the analysis: (1) the transition to inactivity; (2) lack of knowledge and confidence; (3) positive exercise experiences; and (4) perspectives on exercise adherence. Lack of confidence and exercise knowledge, coupled with negative perceptions about physical capabilities after an MS diagnosis, are clear barriers to exercise participation in PwMS. These issues are not being adequately addressed as part of the health care pathway or in community settings. Perceptions of improved posture, ability to overcome everyday difficulties, acute mood enhancements during and after exercise, and increased opportunities for social interaction were among the reported benefits of exercise participation. Despite the provision of a personally tailored exercise plan and use of cognitive behavioral strategies, self-directed exercise continued to present challenges to PwMS, and the importance of seeking cost-effective ways to maintain motivational support was implicit in participant responses. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  17. Engineering drought tolerant tomato plants over-expressing BcZAT12 gene encoding a C₂H₂ zinc finger transcription factor.

    Science.gov (United States)

    Rai, Avinash Chandra; Singh, Major; Shah, Kavita

    2013-01-01

    Efficient genetic transformation of cotyledonary explants of tomato (Solanum lycopersicum, cv. H-86, Kashi vishesh) was obtained. Disarmed Agrobacterium tumifaciens strain GV 3101 was used in conjugation with binary vector pBinAR containing a construct consisting of the coding sequence of the BcZAT12 gene under the regulatory control of the stress inducible Bclea1a promoter. ZAT12 encodes a C₂H₂ zinc finger protein which confers multiple abiotic stress tolerance to plants. Integration of ZAT12 gene into nuclear genome of individual kanamycin resistant transformed T₀ tomato lines was confirmed by Southern blot hybridization with segregation analysis of T(1) plants showing Mendelian inheritance of the transgene. Expression of ZAT12 in drought-stressed transformed tomato lines was verified in T₂ generation plants using RT-PCR. Of the six transformed tomato lines (ZT1-ZT6) the transformants ZT1 and ZT5 showed maximum expression of BcZAT12 gene transcripts when exposed to 7 days drought stress. Analysis of relative water content (RWC), electrolyte leakage (EL), chlorophyll colour index (CCI), H₂O₂ level and catalase activity suggested that tomato BcZAT12 transformants ZT1 and ZT5 have significantly increased levels of drought tolerance. These results suggest that BcZAT12 transformed tomato cv. H-86 has real potential for molecular breeding programs aimed at augmenting yield of tomato in regions affected with drought stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Cloning, over-expression and purification of Pseudomonas aeruginosa murC encoding uridine diphosphate N-acetylmuramate: L-alanine ligase.

    Science.gov (United States)

    El Zoeiby, A; Sanschagrin, F; Lamoureux, J; Darveau, A; Levesque, R C

    2000-02-15

    We cloned and sequenced the murC gene from Pseudomonas aeruginosa encoding a protein of 53 kDa. Multiple alignments with 20 MurC peptide sequences from different bacteria confirmed the presence of highly conserved regions having sequence identities ranging from 22-97% including conserved motifs for ATP-binding and the active site of the enzyme. Genetic complementation was done in Escherichia coli (murCts) suppressing the lethal phenotype. The murC gene was subcloned into the expression vector pET30a and overexpressed in E. coli BL21(lambdaDE3). Three PCR cloning strategies were used to obtain the three recombinant plasmids for expression of the native MurC, MurC His-tagged at N-terminal and at C-terminal, respectively. MurC His-tagged at C-terminal was chosen for large scale production and protein purification in the soluble form. The purification was done in a single chromatographic step on an affinity nickel column and obtained in mg quantities at 95% homogeneity. MurC protein was used to produce monoclonal antibodies for epitope mapping and for assay development in high throughput screenings. Detailed studies of MurC and other genes of the bacterial cell cycle will provide the reagents and strain constructs for high throughput screening and for design of novel antibacterials.

  19. A Canadian qualitative study exploring the diversity of the experience of family caregivers of older adults with multiple chronic conditions using a social location perspective.

    Science.gov (United States)

    Williams, Allison; Sethi, Bharati; Duggleby, Wendy; Ploeg, Jenny; Markle-Reid, Maureen; Peacock, Shelley; Ghosh, Sunita

    2016-03-02

    A little-studied issue in the provision of care at home by informal caregivers is the increase in older adult patients with chronic illness, and more specifically, multiple chronic conditions (MCC). We know little about the caregiving experience for this population, particularly as it is affected by social location, which refers to either a group's or individual's place/location in society at a given time, based on their intersecting demographics (age, gender, education, race, immigration status, geography, etc.). We have yet to fully comprehend the combined influence of these intersecting axes on caregivers' health and wellbeing, and attempt to do this by using an intersectionality approach in answering the following research question: How does social location influence the experience of family caregivers of older adults with MCC? The data presented herein is a thematic analysis of a qualitative sub-set of a large two-province study conducted using a repeated-measures embedded mixed method design. A survey sub-set of 20 survey participants per province (n = 40 total) were invited to participate in a semi-structured interview. In the first stage of data analysis, Charmaz's (2006) Constructivist Grounded Theory Method (CGTM) was used to develop initial codes, focused codes, categories and descriptive themes. In the second and the third stages of analysis, intersectionality was used to develop final analytical themes. The following four themes describe the overall study findings: (1) Caregiving Trajectory, where three caregiving phases were identified; (2) Work, Family, and Caregiving, where the impact of caregiving was discussed on other areas of caregivers' lives; (3) Personal and Structural Determinants of Caregiving, where caregiving sustainability and coping were deliberated, and; (4) Finding Meaning/Self in Caregiving, where meaning-making was highlighted. The intersectionality approach presented a number of axes of diversity as comparatively more important

  20. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase.

    Science.gov (United States)

    Chan, Ben C L; Ip, Margaret; Lau, Clara B S; Lui, S L; Jolivalt, Claude; Ganem-Elbaz, Carine; Litaudon, Marc; Reiner, Neil E; Gong, Huansheng; See, Raymond H; Fung, K P; Leung, P C

    2011-09-01

    Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of β-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms. A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities of baicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined. In the checkerboard dilution test and time-kill assay, baicalein at 16 μg/ml could synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner. Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Damage to tungsten macro-brush targets under multiple ELM-like heat loads. Experiments vs. numerical simulations and extrapolation to ITER

    Energy Technology Data Exchange (ETDEWEB)

    Bazylev, B.; Landman, I. [Forschungszentrum Karlsruhe (Germany). IHM; Janeschitz, G. [Forschungszentrum Karlsruhe (DE). Fusion EURATOM] (and others)

    2007-07-01

    Operation of ITER at high fusion gain is assumed to be the H-mode. A characteristic feature of this regime is the transient release of energy from the confined plasma onto PFCs by multiple ELMs (about 104 ELMs per ITER discharge), which can play a determining role in the erosion rate and lifetime of these components. The expected energy heat loads on the ITER divertor during Type I ELM are in range 0.5-4 MJ/m{sup 2} in timescales of 0.3-0.6 ms. Tungsten macro-brush armour (W-brushes) is foreseen as one of plasma facing components (PFC) for ITER divertor and dome. During the intense transient events in ITER the surface melting, melt motion, melt splashing and evaporation are seen as the main mechanisms of W erosion. The expected erosion of the ITER plasma facing components under transient energy loads can be properly estimated by numerical simulations validated against target erosion of the experiments at the plasma gun facility QSPA-T. Within the collaboration established between EU fusion programme and the Russian Federation, W-brush targets (produced either from pure tungsten or tungsten with 1% of La{sub 2}O{sub 3}) manufactured according to the EU specifications for the ITER divertor targets, have been exposed to multiple ITER ELM-like loads in plasma gun facilities at TRINITI in the range 0.5 - 2.2 MJ/m2 with pulse duration of 0.5 ms. The measured material erosion data have been used to validate the codes MEMOS and PHEMOBRID. Numerical simulations, including 3D-simulations (codes MEMOS and PHEMOBRID), carried out for the conditions of the QSPA-T experiments with heat loads in the range 0.5-2.2 MJ/m{sup 2} and the timescale 0.5 ms demonstrated a rather good agreement with the data obtained at the plasma gun facility QSPA: melting of brush edges at low heat loads, intense melt motion and bridge formation caused by the Rayleigh-Taylor instability at heat loads Q>1.3 MJ/m{sup 2}. The melt splashing generated by the Kelvin-Helmholtz, and Rayleigh

  2. Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience.

    Science.gov (United States)

    Cerchione, Claudio; Nappi, Davide; Pareto, Anna E; Romano, Alessandra; Martinelli, Vincenzo; Picardi, Marco; Pane, Fabrizio; Catalano, Lucio

    2018-04-01

    Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.

  3. First clinical experience with a multiple region of interest registration and correction method in radiotherapy of head-and-neck cancer patients

    International Nuclear Information System (INIS)

    Beek, Suzanne van; Kranen, Simon van; Mencarelli, Angelo; Remeijer, Peter; Rasch, Coen; Herk, Marcel van; Sonke, Jan-Jakob

    2010-01-01

    Purpose: To discuss the first clinical experience with a multiple region of interest (mROI) registration and correction method for high-precision radiotherapy of head-and-neck cancer patients. Materials and methods: 12-13 3D rectangular-shaped ROIs were automatically placed around bony structures on the planning CT scans (n = 50 patients) which were individually registered to subsequent CBCT scans. mROI registration was used to quantify global and local setup errors. The time required to perform the mROI registration was compared with that of a previously used single-ROI method. The number of scans with residual local setup error exceeding 5 mm/5 deg. (warnings) was scored together with the frequency ROIs exceeding these limits for three or more consecutive imaging fractions (systematic errors). Results: In 40% of the CBCT scans, one or more ROI-registrations exceeded the 5 mm/5 deg.. Most warnings were seen in ROI 'hyoid', 31% of the rotation warnings and 14% of the translation warnings. Systematic errors lead to 52 consults of the treating physician. The preparation and registration time was similar for both registration methods. Conclusions: The mROI registration method is easy to use with little extra workload, provides additional information on local setup errors, and helps to select patients for re-planning.

  4. Faith as a Resource in Patients with Multiple Sclerosis Is Associated with a Positive Interpretation of Illness and Experience of Gratitude/Awe

    Directory of Open Access Journals (Sweden)

    Arndt Büssing

    2013-01-01

    Full Text Available The aim of this cross-sectional anonymous survey with standardized questionnaires was to investigate which resources to cope were used by patients with multiple sclerosis (MS. We focussed on patients' conviction that their faith might be a strong hold in difficult times and on their engagement in different forms of spirituality. Consecutively 213 German patients (75% women; mean age 43 ± 11 years were enrolled. Fifty-five percent regarded themselves as neither religious nor spiritual (R−S−, while 31% describe themselves as religious. For 29%, faith was a strong hold in difficult times. This resource was neither related to patients' EDSS scores, and life affections, fatigue, negative mood states, life satisfaction nor to Positive attitudes. Instead it was moderately associated with a Reappraisal strategy (i.e., and positive interpretation of illness and experience of gratitude/awe. Compared to spiritual/religious patients, R−S− individuals had significantly (P<.0001 lower Reappraisal scores and lower engagement in specific forms of spiritual practices. The ability to reflect on what is essential in life, to appreciate and value life, and also the conviction that illness may have meaning and could be regarded as a chance for development was low in R−S− individuals which either may have no specific interest or are less willing to reflect these issues.

  5. [Over-expression of miR-151a-3p inhibits proliferation and migration of PC-3 prostate cancer cells].

    Science.gov (United States)

    Zhang, Yi; Hao, Tongtong; Zhang, Han; Wei, Pengtao; Li, Xiaohui

    2018-03-01

    Objective To observe the effect of microRNA-151a-3p (miR-151a-3p) up-regulation on the proliferation and migration of prostate cancer cells and explore the possible molecular mechanism. Methods The expression of miR-151a-3p in PC-3M, C4-2B, 22RV1, DU-145, PC-3, LNCap human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time fluorescence quantitative PCR. PC-3 cells with the lowest expression of miR-151a-3p were used for subsequent experiments. Bioinformatics and dual-luciferase reporter assay were performed to predict and test potential target genes of miR-151a-3p. The miR-151a-3p mimics or negative control microRNAs (miR-NCs) were transfected into PC-3 cells. Real-time fluorescence quantitative PCR was used to detect the expression of miR-151a-3p and potential target gene mRNA. The protein expressions of target genes and downstream signaling pathway proteins were analyzed by Western blotting. The proliferation of PC-3 cells was examined by MTT assay, and the migration of PC-3 cells was detected by Transwell TM assay. Results The expression level of miR-151a-3p in the prostate cancer cells was significantly lower than that in RWPE-1 normal human prostate epithelial cells. PC-3 cells had the lowest expression level of miR-151a-3p. The bioinformatics and dual-luciferase reporter assay showed that NEK2 was the potential target gene for miR-151a-3p. After transfection with miR-151a-3p mimics, the expression of miR-151a-3p in PC-3 cells significantly increased and the expression of NEK2 mRNA significantly decreased. The protein expressions of PI3K-AKT-mTOR signaling pathway were also reduced. Up-regulation of miR-151a-3p significantly inhibited the proliferation and migration of PC-3 cells. Conclusion The expression of miR-151a-3p is reduced in prostate cancer cells. Up-regulation of miR-151a-3p can inhibit the proliferation and migration of P-3 in prostate cancer by decreasing the expression of NEK2 and PI3K

  6. Cocaine- and amphetamine-regulated transcript peptide in the nucleus accumbens shell inhibits cocaine-induced locomotor sensitization to transient over-expression of α-Ca2+ /calmodulin-dependent protein kinase II.

    Science.gov (United States)

    Xiong, Lixia; Meng, Qing; Sun, Xi; Lu, Xiangtong; Fu, Qiang; Peng, Qinghua; Yang, Jianhua; Oh, Ki-Wan; Hu, Zhenzhen

    2018-01-04

    Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine-induced locomotor activity is related to a reduction in cocaine-enhanced phosphorylated Ca 2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca 2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus-transfected CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca 2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-over-expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine-induced locomotor sensitization. © 2018 International Society for Neurochemistry.

  7. Stable GPR101 over-Expressing Cell Lines As an Invaluable Tool for Functional Studies, Ligand Screening, and the Identification of Deregulated Genes/Pathways in Patients with X-Linked Acrogigantism

    OpenAIRE

    Trivellin, Giampaolo; Janjic, Maria; Larco, Darwin; Tomic, Melanija; Daly, Adrian; Palmeira, Leonor; Faucz; BECKERS, Albert; Wu, T John; Calebiro, Davide; Stojilkovic, Stanko; Stratakis, Constantine

    2017-01-01

    Background: GPR101 is an orphan G protein-coupled receptor (GPCR) that is duplicated in patients with X-linked acrogigantism (X-LAG) and over-expressed in their GH- and PRL-secreting tumors. GPR101 is a constitutively active GPCR that strongly activates the cAMP pathway. To elucidate the mechanisms through which GPR101 causes GH over-secretion we generated HEK293 and GH/PRL-secreting (GH3) cells with stable GPR101 expression. Methods: Both cell lines were created via direct integration of ...

  8. The Experiences and Consequences of a Multiple Trauma Event from the Perspective of the Patient Experiencia del paciente politraumatizado y sus consecuencias Experiência do paciente politraumatizado e suas consequências

    Directory of Open Access Journals (Sweden)

    Luciana Paiva

    2010-12-01

    Full Text Available This was an ethnographic investigation with the aim of comprehending the meanings of the trauma experience among multiple trauma patients. The following techniques were used for data collection: direct observation, semi-structured interview and field diary. Biographical narratives were obtained from eleven trauma victims, and ten relatives as secondary informants. The data analysis considered the set of data of each participant and all data of all subjects, searching for differences and similarities. The meanings attributed to the trauma experience are associated with interrelated feelings of fear, insecurity, anger, vulnerability and suffering and to the meanings of quality of life that converge to valorize health and work appreciation and support by social networks. This analysis shows that the concepts and experiences of the trauma are conditioning factors of the health-disease process and they are essential in planning public health actions to meet the needs of individuals.Se trata de una investigación etnográfica realizada con el objetivo de comprender los significados de la experiencia del trauma en pacientes politraumatizados. Fueron utilizadas las siguientes técnicas de recolección de datos: observación directa, entrevista semi-estructurada y diario de campo. Obtuvimos narraciones biográficas de 11 personas víctimas de traumas y 10 familiares, como informantes secundarios. El análisis de los datos consideró el conjunto de los datos de cada participante y el todo de los datos de todos los sujetos, buscando diferencias y similitudes. Los sentidos atribuidos a la experiencia del trauma se asocian a sentimientos interrelacionados de miedo, inseguridad, rabia, vulnerabilidad y sufrimiento y a los significados de calidad de vida que convergen para la valorización de la salud, trabajo y apoyo por las redes sociales. Este análisis muestra que las concepciones y vivencias del trauma son factores condicionantes del proceso salud

  9. Experiences of nurse practitioners and medical practitioners working in collaborative practice models in primary healthcare in Australia - a multiple case study using mixed methods.

    Science.gov (United States)

    Schadewaldt, Verena; McInnes, Elizabeth; Hiller, Janet E; Gardner, Anne

    2016-07-29

    In 2010 policy changes were introduced to the Australian healthcare system that granted nurse practitioners access to the public health insurance scheme (Medicare) subject to a collaborative arrangement with a medical practitioner. These changes facilitated nurse practitioner practice in primary healthcare settings. This study investigated the experiences and perceptions of nurse practitioners and medical practitioners who worked together under the new policies and aimed to identify enablers of collaborative practice models. A multiple case study of five primary healthcare sites was undertaken, applying mixed methods research. Six nurse practitioners, 13 medical practitioners and three practice managers participated in the study. Data were collected through direct observations, documents and semi-structured interviews as well as questionnaires including validated scales to measure the level of collaboration, satisfaction with collaboration and beliefs in the benefits of collaboration. Thematic analysis was undertaken for qualitative data from interviews, observations and documents, followed by deductive analysis whereby thematic categories were compared to two theoretical models of collaboration. Questionnaire responses were summarised using descriptive statistics. Using the scale measurements, nurse practitioners and medical practitioners reported high levels of collaboration, were highly satisfied with their collaborative relationship and strongly believed that collaboration benefited the patient. The three themes developed from qualitative data showed a more complex and nuanced picture: 1) Structures such as government policy requirements and local infrastructure disadvantaged nurse practitioners financially and professionally in collaborative practice models; 2) Participants experienced the influence and consequences of individual role enactment through the co-existence of overlapping, complementary, traditional and emerging roles, which blurred perceptions of

  10. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  11. MULTIPLE OBJECTS

    Directory of Open Access Journals (Sweden)

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  12. The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

    Science.gov (United States)

    Chen, Shi; Zhang, Jia-Qiang; Chen, Jiang-Zhi; Chen, Hui-Xing; Qiu, Fu-Nan; Yan, Mao-Lin; Chen, Yan-Ling; Peng, Cheng-Hong; Tian, Yi-Feng; Wang, Yao-Dong

    2017-09-01

    This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Positive feedback regulation of a Lycium chinense-derived VDE gene by drought-induced endogenous ABA, and over-expression of this VDE gene improve drought-induced photo-damage in Arabidopsis.

    Science.gov (United States)

    Guan, Chunfeng; Ji, Jing; Zhang, Xuqiang; Li, Xiaozhou; Jin, Chao; Guan, Wenzhu; Wang, Gang

    2015-03-01

    Violaxanthin de-epoxidase (VDE) plays an important role in protecting the photosynthetic apparatus from photo-damage by dissipating excessively absorbed light energy as heat, via the conversion of violaxanthin (V) to intermediate product antheraxanthin (A) and final product zeaxanthin (Z) under light stress. We have cloned a VDE gene (LcVDE) from Lycium chinense, a deciduous woody perennial halophyte, which can grow in a large variety of soil types. The amino acid sequence of LcVDE has high homology with VDEs in other plants. Under drought stress, relative expression of LcVDE and the de-epoxidation ratio (Z+0.5A)/(V+A+Z) increased rapidly, and non-photochemical quenching (NPQ) also rose. Interestingly, these elevations induced by drought stress were reduced by the topical administration of abamine SG, a potent ABA inhibitor via inhibition of NCED in the ABA synthesis pathway. Until now, little has been done to explore the relationship between endogenous ABA and the expression of VDE genes. Since V serves as a common precursor for ABA, these data support the possible involvement of endogenous ABA in the positive feedback regulation of LcVDE gene expression in L. chinense under drought stress. Moreover, the LcVDE may be involved in modulating the level of photosynthesis damage caused by drought stress. Furthermore, the ratio of (Z+0.5A)/(V+A+Z) and NPQ increased more in transgenic Arabidopsis over-expressing LcVDE gene than the wild types under drought stress. The maximum quantum yield of primary photochemistry of PSII (Fv/Fm) in transgenic Arabidopsis decreased more slowly during the stressed period than that in wild types under the same conditions. Furthermore, transgenic Arabidopsis over-expressing LcVDE showed increased tolerance to drought stress. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Effectiveness and user experience of web-based interventions for increasing physical activity in people with multiple sclerosis: a comprehensive systematic review protocol.

    Science.gov (United States)

    Dennett, Rachel; Coulter, Elaine; Paul, Lorna; Freeman, Jennifer

    2016-11-01

    The overall aim of this comprehensive systematic review is to explore the use of web-based interventions for increasing physical activity levels in people with a diagnosis of multiple sclerosis (MS).The quantitative objectives are to identify:The qualitative objectives are to.

  15. The Part-Time Student Role: Implications for the Emotional Experience of Managing Multiple Roles amongst Hong Kong Public Health Nurses.

    Science.gov (United States)

    Shiu, Ann Tak-Ying

    1999-01-01

    Nine public-health nurses studying part time and 11 other nurses sampled their mood states randomly over seven days. The part-time student role created additional strain for nurses with children. The stress of managing multiple roles was greatest when both work and nonwork role responsibilities were heavy. (SK)

  16. Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience

    OpenAIRE

    Casamento, K.; Laverty, A.; Wilsher, M.; Twiss, J.; Gabbay, E.; Glaspole, I.; Jaffe, A.

    2016-01-01

    Background We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. Methods A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were s...

  17. Conservative two-step procedure including uterine artery embolization with embosphere and surgical myomectomy for the treatment of multiple fibroids: Preliminary experience

    International Nuclear Information System (INIS)

    Malartic, Cécile; Morel, Olivier; Fargeaudou, Yann; Le Dref, Olivier; Fazel, Afchine; Barranger, Emmanuel; Soyer, Philippe

    2012-01-01

    Objective: To evaluate the feasibility and safety of combined uterine artery embolization (UAE) using embosphere and surgical myomectomy as an alternative to radical hysterectomy in premenopausal women with multiple fibroids. Materials and methods: Mid-term clinical outcome (mean, 25 months) of 12 premenopausal women (mean age, 38 years) with multiple and large symptomatic fibroids who desired to retain their uterus and who were treated using combined UAE and surgical myomectomy were retrospectively analyzed. In all women, UAE alone was contraindicated because of large (>10 cm) or subserosal or submucosal fibroids and myomectomy alone was contraindicated because of too many (>10) fibroids. Results: UAE and surgical myomectomy were successfully performed in all women. Myomectomy was performed using laparoscopy (n = 6), open laparotomy (n = 3), hysteroscopy (n = 2), or laparoscopy and hysteroscopy (n = 1). Mean serum hemoglobin level drop was 0.97 g/dL and no blood transfusion was needed. No immediate complications were observed and all women reported resumption of normal menses. During a mean follow-up period of 25 months (range, 14–37 months), complete resolution of initial symptoms along with decrease in uterine volume (mean, 48%) was observed in all women. No further hysterectomy was required in any woman. Conclusion: In premenopausal women with multiple fibroids, the two-step procedure is safe and effective alternative to radical hysterectomy, which allows preserving the uterus. Further prospective studies, however, should be done to determine the actual benefit of this combined approach on the incidence of subsequent pregnancies.

  18. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  19. miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer.

    Science.gov (United States)

    Corcoran, Claire; Rani, Sweta; Breslin, Susan; Gogarty, Martina; Ghobrial, Irene M; Crown, John; O'Driscoll, Lorraine

    2014-03-24

    While the treatment of HER2 over-expressing breast cancer with recent HER-targeted drugs has been highly effective for some patients, primary (also known as innate) or acquired resistance limits the success of these drugs. microRNAs have potential as diagnostic, prognostic and predictive biomarkers, as well as replacement therapies. Here we investigated the role of microRNA-630 (miR-630) in breast cancer progression and as a predictive biomarker for response to HER-targeting drugs, ultimately yielding potential as a therapeutic approach to add value to these drugs. We investigated the levels of intra- and extracellular miR-630 in cells and conditioned media from breast cancer cell lines with either innate- or acquired- resistance to HER-targeting lapatinib and neratinib, compared to their corresponding drug sensitive cell lines, using qPCR. To support the role of miR-630 in breast cancer, we examined the clinical relevance of this miRNA in breast cancer tumours versus matched peritumours. Transfection of miR-630 mimics and inhibitors was used to manipulate the expression of miR-630 to assess effects on response to HER-targeting drugs (lapatinib, neratinib and afatinib). Other phenotypic changes associated with cellular aggressiveness were evaluated by motility, invasion and anoikis assays. TargetScan prediction software, qPCR, immunoblotting and ELISAs, were used to assess miR-630's regulation of mRNA, proteins and their phosphorylated forms. We established that introducing miR-630 into cells with innate- or acquired- resistance to HER-drugs significantly restored the efficacy of lapatinib, neratinib and afatinib; through a mechanism which we have determined to, at least partly, involve miR-630's regulation of IGF1R. Conversely, we demonstrated that blocking miR-630 induced resistance/insensitivity to these drugs. Cellular motility, invasion, and anoikis were also observed as significantly altered by miR-630 manipulation, whereby introducing miR-630 into cells

  20. Amplification of the Ect2 proto-oncogene and over-expression of Ect2 mRNA and protein in nickel compound and methylcholanthrene-transformed 10T1/2 mouse fibroblast cell lines

    International Nuclear Information System (INIS)

    Clemens, Farrah; Verma, Rini; Ramnath, Jamuna; Landolph, Joseph R.

    2005-01-01

    Occupational exposure of humans to mixtures of insoluble and soluble nickel (Ni) compounds correlates with increased incidences of lung, sinus, and pharyngeal tumors. Specific insoluble Ni compounds are carcinogenic to animals by inhalation and induce morphological and neoplastic transformation of cultured rodent cells. Our objectives were to (1) understand mechanisms of nickel ion-induced cell transformation, hence carcinogenesis and (2) develop biomarkers of nickel ion exposure and nickel ion-induced cell transformation. We isolated mRNAs from green nickel oxide (NiO), crystalline nickel monosulfide (NiS), and 3-methylcholanthrene (MCA) transformed C3H/10T1/2 Cl 8 cell lines, and determined by mRNA differential display that nine mRNA fragments were differentially expressed between Ni transformed and non-transformed 10T1/2 cell lines. Fragment R2-5 was expressed at higher steady-state levels in the transformed cell lines. R2-5 had 100% sequence identity to part of the coding region of Ect2, a mouse proto-oncogene encoding a GDP-GTP exchange factor. The 3.9-kb Ect2 transcript was expressed at 1.6- to 3.6-fold higher steady-state levels in four Ni transformed, and in two MCA-transformed, cell lines. Ect2 protein was expressed at 3.0- to 4.5-fold higher steady-state levels in Ni-transformed and in MCA-transformed cell lines. The Ect2 gene was amplified by 3.5- to 10-fold in Ni transformed, and by 2.5- to 3-fold in MCA transformed cell lines. Binding of nickel ions to enzymes of DNA synthesis likely caused amplification of the Ect2 gene. Ect2 gene amplification and over-expression of Ect2 mRNA and protein can cause microtubule disassembly and cytokinesis, contributing to induction and maintenance of morphological, anchorage-independent, and neoplastic transformation of these cell lines. Over-expression of Ect2 protein is a useful biomarker to detect exposure to nickel compounds and nickel ion-induced morphological and neoplastic cell transformation

  1. Multiple homicides.

    Science.gov (United States)

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  2. Search for new phenomena in a lepton plus high jet multiplicity final state with the ATLAS experiment using $\\sqrt{s}$ = 13 TeV proton-proton collision data

    CERN Document Server

    Aaboud, Morad; ATLAS Collaboration; Abbott, Brad; Abdinov, Ovsat; Abeloos, Baptiste; Abidi, Syed Haider; AbouZeid, Ossama; Abraham, Nicola; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adachi, Shunsuke; Adamczyk, Leszek; Adelman, Jahred; Adersberger, Michael; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Agheorghiesei, Catalin; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akatsuka, Shunichi; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akilli, Ece; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albicocco, Pietro; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Ali, Babar; Aliev, Malik; Alimonti, Gianluca; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allen, Benjamin William; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Alshehri, Azzah Aziz; Alstaty, Mahmoud; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Angerami, Aaron; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antel, Claire; Antonelli, Mario; Antonov, Alexey; Antrim, Daniel Joseph; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Araujo Ferraz, Victor; Arce, Ayana; Ardell, Rose Elisabeth; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Armitage, Lewis James; Arnaez, Olivier; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Artz, Sebastian; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Augsten, Kamil; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baas, Alessandra; Baca, Matthew John; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Bagnaia, Paolo; Bahmani, Marzieh; Bahrasemani, Sina; Baines, John; Bajic, Milena; Baker, Oliver Keith; Baldin, Evgenii; Balek, Petr; Balli, Fabrice; Balunas, William Keaton; Banas, Elzbieta; Banerjee, Swagato; Bannoura, Arwa A E; Barak, Liron; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisits, Martin-Stefan; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska-Blenessy, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barranco Navarro, Laura; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Bechtle, Philip; Beck, Hans~Peter; Beck, Helge Christoph; Becker, Kathrin; Becker, Maurice; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bedognetti, Matteo; Bee, Christopher; Beermann, Thomas; Begalli, Marcia; Begel, Michael; Behr, Janna Katharina; Bell, Andrew Stuart; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Belyaev, Nikita; Benary, Odette; Benchekroun, Driss; Bender, Michael; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez, Jose; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Beringer, Jürg; Berlendis, Simon; Bernard, Nathan Rogers; Bernardi, Gregorio; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertram, Iain Alexander; Bertsche, Carolyn; Bertsche, David; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethani, Agni; Bethke, Siegfried; Bevan, Adrian John; Beyer, Julien-christopher; Bianchi, Riccardo-Maria; Biebel, Otmar; Biedermann, Dustin; Bielski, Rafal; Bierwagen, Katharina; Biesuz, Nicolo Vladi; Biglietti, Michela; Billoud, Thomas Remy Victor; Bilokon, Halina; Bindi, Marcello; Bingul, Ahmet; Bini, Cesare; Biondi, Silvia; Bisanz, Tobias; Bittrich, Carsten; Bjergaard, David Martin; Black, Curtis; Black, James; Black, Kevin; Blair, Robert; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blue, Andrew; Blum, Walter; Blumenschein, Ulrike; Blunier, Sylvain; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Boerner, Daniela; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bokan, Petar; Bold, Tomasz; Boldyrev, Alexey; Bolz, Arthur Eugen; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Bortfeldt, Jonathan; Bortoletto, Daniela; Bortolotto, Valerio; Boscherini, Davide; Bosman, Martine; Bossio Sola, Jonathan David; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Boutle, Sarah Kate; Boveia, Antonio; Boyd, James; Boyko, Igor; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Briglin, Daniel Lawrence; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Broughton, James; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruni, Alessia; Bruni, Graziano; Bruni, Lucrezia Stella; Brunt, Benjamin; Bruschi, Marco; Bruscino, Nello; Bryant, Patrick; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Budagov, Ioulian; Buehrer, Felix; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burch, Tyler James; Burdin, Sergey; Burgard, Carsten Daniel; Burger, Angela Maria; Burghgrave, Blake; Burka, Klaudia; Burke, Stephen; Burmeister, Ingo; Burr, Jonathan Thomas Peter; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Butler, John; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabrera Urbán, Susana; Caforio, Davide; Cairo, Valentina; Cakir, Orhan; Calace, Noemi; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Callea, Giuseppe; Caloba, Luiz; Calvente Lopez, Sergio; Calvet, David; Calvet, Samuel; Calvet, Thomas Philippe; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminal Armadans, Roger; Camincher, Clement; Campana, Simone; Campanelli, Mario; Camplani, Alessandra; Campoverde, Angel; Canale, Vincenzo; Cano Bret, Marc; Cantero, Josu; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Carbone, Ryne Michael; Cardarelli, Roberto; Cardillo, Fabio; Carli, Ina; Carli, Tancredi; Carlino, Gianpaolo; Carlson, Benjamin Taylor; Carminati, Leonardo; Carney, Rebecca; Caron, Sascha; Carquin, Edson; Carrá, Sonia; Carrillo-Montoya, German D; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Casper, David William; Castelijn, Remco; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavallaro, Emanuele; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Celebi, Emre; Ceradini, Filippo; Cerda Alberich, Leonor; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chan, Stephen Kam-wah; Chan, Wing Sheung; Chan, Yat Long; Chang, Philip; Chapman, John Derek; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Che, Siinn; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Shenjian; Chen, Shion; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Huajie; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Cheu, Elliott; Cheung, Kingman; Chevalier, Laurent; Chiarella, Vitaliano; Chiarelli, Giorgio; Chiodini, Gabriele; Chisholm, Andrew; Chitan, Adrian; Chiu, Yu Him Justin; Chizhov, Mihail; Choi, Kyungeon; Chomont, Arthur Rene; Chouridou, Sofia; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chu, Ming Chung; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocca, Claudia; Ciocio, Alessandra; Cirotto, Francesco; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Michael; Clark, Philip James; Clarke, Robert; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Colasurdo, Luca; Cole, Brian; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Constantinescu, Serban; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper-Sarkar, Amanda; Cormier, Felix; Cormier, Kyle James Read; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Crawley, Samuel Joseph; Creager, Rachael; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cueto, Ana; Cuhadar Donszelmann, Tulay; Cukierman, Aviv Ruben; Cummings, Jane; Curatolo, Maria; Cúth, Jakub; Czodrowski, Patrick; D'amen, Gabriele; D'Auria, Saverio; D'eramo, Louis; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dado, Tomas; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey; Daneri, Maria Florencia; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Dann, Nicholas Stuart; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Daubney, Thomas; Davey, Will; David, Claire; Davidek, Tomas; Davis, Douglas; Davison, Peter; Dawe, Edmund; Dawson, Ian; De, Kaushik; de Asmundis, Riccardo; De Benedetti, Abraham; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Maria, Antonio; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vasconcelos Corga, Kevin; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Dehghanian, Nooshin; Deigaard, Ingrid; Del Gaudio, Michela; Del Peso, Jose; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delporte, Charles; Delsart, Pierre-Antoine; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Denysiuk, Denys; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Dette, Karola; Devesa, Maria Roberta; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Bello, Francesco Armando; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Clemente, William Kennedy; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Micco, Biagio; Di Nardo, Roberto; Di Petrillo, Karri Folan; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Díez Cornell, Sergio; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dolejsi, Jiri; Dolezal, Zdenek; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Du, Yanyan; Duarte-Campderros, Jorge; Dubreuil, Arnaud; Duchovni, Ehud; Duckeck, Guenter; Ducourthial, Audrey; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudder, Andreas Christian; Duffield, Emily Marie; Duflot, Laurent; Dührssen, Michael; Dumancic, Mirta; Dumitriu, Ana Elena; Duncan, Anna Kathryn; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dutta, Baishali; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; El Kosseifi, Rima; Ellajosyula, Venugopal; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Ennis, Joseph Stanford; Erdmann, Johannes; Ereditato, Antonio; Ernst, Michael; Errede, Steven; Escalier, Marc; Escobar, Carlos; Esposito, Bellisario; Estrada Pastor, Oscar; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Ezzi, Mohammed; Fabbri, Federica; Fabbri, Laura; Fabiani, Veronica; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farina, Christian; Farina, Edoardo Maria; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fawcett, William James; Fayard, Louis; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenton, Michael James; Fenyuk, Alexander; Feremenga, Last; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Flaschel, Nils; Fleck, Ivor; Fleischmann, Philipp; Fletcher, Rob Roy MacGregor; Flick, Tobias; Flierl, Bernhard Matthias; Flores Castillo, Luis; Flowerdew, Michael; Forcolin, Giulio Tiziano; Formica, Andrea; Förster, Fabian Alexander; Forti, Alessandra; Foster, Andrew Geoffrey; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; Fressard-Batraneanu, Silvia; Freund, Benjamin; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fusayasu, Takahiro; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gach, Grzegorz; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Louis Guillaume; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Ganguly, Sanmay; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; García, Carmen; García Navarro, José Enrique; García Pascual, Juan Antonio; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gascon Bravo, Alberto; Gasnikova, Ksenia; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Gee, Norman; Geisen, Jannik; Geisen, Marc; Geisler, Manuel Patrice; Gellerstedt, Karl; Gemme, Claudia; Genest, Marie-Hélène; Geng, Cong; Gentile, Simonetta; Gentsos, Christos; George, Simon; Gerbaudo, Davide; Gershon, Avi; Geß{}ner, Gregor; Ghasemi, Sara; Ghneimat, Mazuza; Giacobbe, Benedetto; Giagu, Stefano; Giannetti, Paola; Gibson, Stephen; Gignac, Matthew; Gilchriese, Murdock; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuli, Francesco; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gkountoumis, Panagiotis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Gama, Rafael; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Giulia; Gonella, Laura; Gongadze, Alexi; González de la Hoz, Santiago; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gottardo, Carlo Alberto; Goudet, Christophe Raymond; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Gozani, Eitan; Graber, Lars; Grabowska-Bold, Iwona; Gradin, Per Olov Joakim; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Gratchev, Vadim; Gravila, Paul Mircea; Gray, Chloe; Gray, Heather; Greenwood, Zeno Dixon; Grefe, Christian; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Grevtsov, Kirill; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Groh, Sabrina; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Grummer, Aidan; Guan, Liang; Guan, Wen; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Gui, Bin; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Guo, Wen; Guo, Yicheng; Gupta, Ruchi; Gupta, Shaun; Gustavino, Giuliano; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Guzik, Marcin Pawel; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Hadef, Asma; Hageböck, Stephan; Hagihara, Mutsuto; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Han, Shuo; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Haney, Bijan; Hanke, Paul; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartmann, Nikolai Marcel; Hasegawa, Makoto; Hasegawa, Yoji; Hasib, Ahmed; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havener, Laura Brittany; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hayakawa, Daiki; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heer, Sebastian; Heidegger, Kim Katrin; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Jochen Jens; Heinrich, Lukas; Heinz, Christian; Hejbal, Jiri; Helary, Louis; Held, Alexander; Hellman, Sten; Helsens, Clement; Henderson, Robert; Heng, Yang; Henkelmann, Steffen; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Herde, Hannah; Herget, Verena; Hernández Jiménez, Yesenia; Herr, Holger; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Herwig, Theodor Christian; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Higashino, Satoshi; Higón-Rodriguez, Emilio; Hildebrand, Kevin; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hils, Maximilian; Hinchliffe, Ian; Hirose, Minoru; Hirschbuehl, Dominic; Hiti, Bojan; Hladik, Ondrej; Hoad, Xanthe; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohn, David; Holmes, Tova Ray; Homann, Michael; Honda, Shunsuke; Honda, Takuya; Hong, Tae Min; Hooberman, Benjamin Henry; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howarth, James; Hoya, Joaquin; Hrabovsky, Miroslav; Hrdinka, Julia; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Qipeng; Hu, Shuyang; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Huo, Peng; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikeno, Masahiro; Ilchenko, Yuriy; Iliadis, Dimitrios; Ilic, Nikolina; Introzzi, Gianluca; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Isacson, Max Fredrik; Ishijima, Naoki; Ishino, Masaya; Ishitsuka, Masaki; Issever, Cigdem; Istin, Serhat; Ito, Fumiaki; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Paul; Jacobs, Ruth Magdalena; Jain, Vivek; Jakobi, Katharina Bianca; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jamin, David Olivier; Jana, Dilip; Jansky, Roland; Janssen, Jens; Janus, Michel; Janus, Piotr Andrzej; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Javurkova, Martina; Jeanneau, Fabien; Jeanty, Laura; Jejelava, Juansher; Jelinskas, Adomas; Jenni, Peter; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Hai; Jiang, Yi; Jiang, Zihao; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Jivan, Harshna; Johansson, Per; Johns, Kenneth; Johnson, Christian; Johnson, William Joseph; Jon-And, Kerstin; Jones, Roger; Jones, Samuel David; Jones, Sarah; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Jovicevic, Jelena; Ju, Xiangyang; Juste Rozas, Aurelio; Köhler, Markus Konrad; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kaji, Toshiaki; Kajomovitz, Enrique; Kalderon, Charles William; Kaluza, Adam; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kanjir, Luka; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kaplan, Laser Seymour; Kar, Deepak; Karakostas, Konstantinos; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karentzos, Efstathios; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kasahara, Kota; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Kato, Chikuma; Katre, Akshay; Katzy, Judith; Kawade, Kentaro; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kay, Ellis; Kazanin, Vassili; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Kendrick, James; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khader, Mazin; Khalil-zada, Farkhad; Khanov, Alexander; Kharlamov, Alexey; Kharlamova, Tatyana; Khodinov, Alexander; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kido, Shogo; Kilby, Callum; Kim, Hee Yeun; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; Kirchmeier, David; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kitali, Vincent; Kiuchi, Kenji; Kivernyk, Oleh; Kladiva, Eduard; Klapdor-Kleingrothaus, Thorwald; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klingl, Tobias; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Köhler, Nicolas Maximilian; Koi, Tatsumi; Kolb, Mathis; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotwal, Ashutosh; Koulouris, Aimilianos; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kourlitis, Evangelos; Kouskoura, Vasiliki; Kowalewska, Anna Bozena; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozakai, Chihiro; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitrii; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Krauss, Dominik; Kremer, Jakub Andrzej; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Jiri; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Kruse, Mark; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuechler, Jan Thomas; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Thorsten; Kukhtin, Victor; Kukla, Romain; Kulchitsky, Yuri; Kuleshov, Sergey; Kulinich, Yakov Petrovich; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kupfer, Tobias; Kuprash, Oleg; Kurashige, Hisaya; Kurchaninov, Leonid; Kurochkin, Yurii; Kurth, Matthew Glenn; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; La Ruffa, Francesco; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lammers, Sabine; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lanfermann, Marie Christine; Lang, Valerie Susanne; Lange, J örn Christian; Langenberg, Robert Johannes; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Lapertosa, Alessandro; Laplace, Sandrine; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Lazovich, Tomo; Lazzaroni, Massimo; Le, Brian; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Quilleuc, Eloi; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne; Lee, Claire Alexandra; Lee, Graham Richard; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Benoit; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Lerner, Giuseppe; Leroy, Claude; Lesage, Arthur; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Dave; Li, Bing; Li, Changqiao; Li, Haifeng; Li, Liang; Li, Qi; Li, Shu; Li, Xingguo; Li, Yichen; Liang, Zhijun; Liberti, Barbara; Liblong, Aaron; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Lindquist, Brian Edward; Lionti, Anthony Eric; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Hao; Liu, Hongbin; Liu, Jesse Kar Kee; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Minghui; Liu, Yanlin; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo, Cheuk Yee; Lo Sterzo, Francesco; Lobodzinska, Ewelina Maria; Loch, Peter; Loebinger, Fred; Loesle, Alena; Loew, Kevin Michael; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan David; Long, Robin Eamonn; Longo, Luigi; Looper, Kristina Anne; Lopez, Jorge; Lopez Mateos, David; Lopez Paz, Ivan; Lopez Solis, Alvaro; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Haonan; Lu, Nan; Lu, Yun-Ju; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luedtke, Christian; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Luzi, Pierre Marc; Lynn, David; Lysak, Roman; Lytken, Else; Lyu, Feng; Lyubushkin, Vladimir; Ma, Hong; Ma, Lian Liang; Ma, Yanhui; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Maček, Boštjan; Machado Miguens, Joana; Madaffari, Daniele; Madar, Romain; Mader, Wolfgang; Madsen, Alexander; Maeda, Junpei; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magerl, Veronika; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majersky, Oliver; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Claire; Maltezos, Stavros; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandić, Igor; Maneira, José; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manousos, Athanasios; Mansoulie, Bruno; Mansour, Jason Dhia; Mantifel, Rodger; Mantoani, Matteo; Manzoni, Stefano; Mapelli, Livio; Marceca, Gino; March, Luis; Marchese, Luigi; Marchiori, Giovanni; Marcisovsky, Michal; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Martensson, Mikael; Marti-Garcia, Salvador; Martin, Christopher Blake; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martinez Outschoorn, Verena; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Lorenzo; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Maznas, Ioannis; Mazza, Simone Michele; Mc Fadden, Neil Christopher; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McClymont, Laurie; McDonald, Emily; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McNamara, Peter Charles; McPherson, Robert; Meehan, Samuel; Megy, Theo Jean; Mehlhase, Sascha; Mehta, Andrew; Meideck, Thomas; Meier, Karlheinz; Meirose, Bernhard; Melini, Davide; Mellado Garcia, Bruce Rafael; Mellenthin, Johannes Donatus; Melo, Matej; Meloni, Federico; Melzer, Alexander; Menary, Stephen Burns; Meng, Lingxin; Meng, Xiangting; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer Zu Theenhausen, Hanno; Miano, Fabrizio; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Minegishi, Yuji; Ming, Yao; Mir, Lluisa-Maria; Mistry, Khilesh; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mizukami, Atsushi; Mjörnmark, Jan-Ulf; Mkrtchyan, Tigran; Mlynarikova, Michaela; Moa, Torbjoern; Mochizuki, Kazuya; Mogg, Philipp; Mohapatra, Soumya; Molander, Simon; Moles-Valls, Regina; Monden, Ryutaro; Mondragon, Matthew Craig; Mönig, Klaus; Monk, James; Monnier, Emmanuel; Montalbano, Alyssa; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Stefanie; Mori, Daniel; Mori, Tatsuya; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moschovakos, Paris; Mosidze, Maia; Moss, Harry James; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Moyse, Edward; Muanza, Steve; Mueller, Felix; Mueller, James; Mueller, Ralph Soeren Peter; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munoz Sanchez, Francisca Javiela; Murray, Bill; Musheghyan, Haykuhi; Muškinja, Miha; Myagkov, Alexey; Myska, Miroslav; Nachman, Benjamin Philip; Nackenhorst, Olaf; Nagai, Koichi; Nagai, Ryo; Nagano, Kunihiro; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Narrias Villar, Daniel Isaac; Naryshkin, Iouri; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nelson, Michael Edward; Nemecek, Stanislav; Nemethy, Peter; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Newman, Paul; Ng, Tsz Yu; Nguyen Manh, Tuan; Nickerson, Richard; Nicolaidou, Rosy; Nielsen, Jason; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nishu, Nishu; Nisius, Richard; Nitsche, Isabel; Nobe, Takuya; Noguchi, Yohei; Nomachi, Masaharu; Nomidis, Ioannis; Nomura, Marcelo Ayumu; Nooney, Tamsin; Nordberg, Markus; Norjoharuddeen, Nurfikri; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nurse, Emily; Nuti, Francesco; O'connor, Kelsey; O'Neil, Dugan; O'Rourke, Abigail Alexandra; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Oleiro Seabra, Luis Filipe; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onogi, Kouta; Onyisi, Peter; Oppen, Henrik; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Pacheco Rodriguez, Laura; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganini, Michela; Paige, Frank; Palacino, Gabriel; Palazzo, Serena; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Panagiotopoulou, Evgenia; Panagoulias, Ilias; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Adam Jackson; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pascuzzi, Vincent; Pasner, Jacob Martin; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Francesca; Pataraia, Sophio; Pater, Joleen; Pauly, Thilo; Pearson, Benjamin; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Penc, Ondrej; Peng, Cong; Peng, Haiping; Penwell, John; Peralva, Bernardo; Perego, Marta Maria; Perepelitsa, Dennis; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petroff, Pierre; Petrolo, Emilio; Petrov, Mariyan; Petrucci, Fabrizio; Pettersson, Nora Emilia; Peyaud, Alan; Pezoa, Raquel; Phillips, Forrest Hays; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Pickering, Mark Andrew; Piegaia, Ricardo; Pilcher, James; Pilkington, Andrew; Pin, Arnaud Willy J; Pinamonti, Michele; Pinfold, James; Pirumov, Hayk; Pitt, Michael; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Pluth, Daniel; Podberezko, Pavel; Poettgen, Ruth; Poggi, Riccardo; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Ponomarenko, Daniil; Pontecorvo, Ludovico; Popeneciu, Gabriel Alexandru; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Poulard, Gilbert; Poulsen, Trine; Poveda, Joaquin; Pozo Astigarraga, Mikel Eukeni; Pralavorio, Pascal; Pranko, Aliaksandr; Prell, Soeren; Price, Darren; Primavera, Margherita; Prince, Sebastien; Proklova, Nadezda; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Puri, Akshat; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Raine, John Andrew; Rajagopalan, Srinivasan; Rangel-Smith, Camila; Rashid, Tasneem; Raspopov, Sergii; Ratti, Maria Giulia; Rauch, Daniel; Rauscher, Felix; Rave, Stefan; Ravinovich, Ilia; Rawling, Jacob Henry; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Reale, Marilea; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reed, Robert; Reeves, Kendall; Rehnisch, Laura; Reichert, Joseph; Reiss, Andreas; Rembser, Christoph; Ren, Huan; Rescigno, Marco; Resconi, Silvia; Resseguie, Elodie Deborah; Rettie, Sebastien; Reynolds, Elliot; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rifki, Othmane; Rijssenbeek, Michael; Rimoldi, Adele; Rimoldi, Marco; Rinaldi, Lorenzo; Ripellino, Giulia; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Rizzi, Chiara; Roberts, Rhys Thomas; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocco, Elena; Roda, Chiara; Rodina, Yulia; Rodriguez Bosca, Sergi; Rodriguez Perez, Andrea; Rodriguez Rodriguez, Daniel; Roe, Shaun; Rogan, Christopher Sean; Røhne, Ole; Roloff, Jennifer; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosien, Nils-Arne; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Jonatan; Rosten, Rachel; Rotaru, Marina; Rothberg, Joseph; Rousseau, David; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryu, Soo; Ryzhov, Andrey; Rzehorz, Gerhard Ferdinand; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saha, Puja; Sahinsoy, Merve; Saimpert, Matthias; Saito, Masahiko; Saito, Tomoyuki; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salazar Loyola, Javier Esteban; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sammel, Dirk; Sampsonidis, Dimitrios; Sampsonidou, Despoina; Sánchez, Javier; Sanchez Martinez, Victoria; Sanchez Pineda, Arturo Rodolfo; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Christian Oliver; Sandhoff, Marisa; Sandoval, Carlos; Sankey, Dave; Sannino, Mario; Sano, Yuta; Sansoni, Andrea; Santoni, Claudio; Santos, Helena; Santoyo Castillo, Itzebelt; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sato, Koji; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Savic, Natascha; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schachtner, Balthasar Maria; Schaefer, Douglas; Schaefer, Leigh; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R Dean; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schier, Sheena; Schildgen, Lara Katharina; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt-Sommerfeld, Korbinian Ralf; Schmieden, Kristof; Schmitt, Christian; Schmitt, Stefan; Schmitz, Simon; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schott, Matthias; Schouwenberg, Jeroen; Schovancova, Jaroslava; Schramm, Steven; Schuh, Natascha; Schulte, Alexandra; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Sciandra, Andrea; Sciolla, Gabriella; Scornajenghi, Matteo; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Semprini-Cesari, Nicola; Senkin, Sergey; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Sessa, Marco; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shaikh, Nabila Wahab; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Shen, Yu-Ting; Sherafati, Nima; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shipsey, Ian Peter Joseph; Shirabe, Shohei; Shiyakova, Mariya; Shlomi, Jonathan; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyed Ruhollah; Shope, David Richard; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sickles, Anne Marie; Sidebo, Per Edvin; Sideras Haddad, Elias; Sidiropoulou, Ourania; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silverstein, Samuel; Simak, Vladislav; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Manuel; Sinervo, Pekka; Sinev, Nikolai; Sioli, Maximiliano; Siragusa, Giovanni; Siral, Ismet; Sivoklokov, Serguei; Sjölin, Jörgen; Skinner, Malcolm Bruce; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Slovak, Radim; Smakhtin, Vladimir; Smart, Ben; Smiesko, Juraj; Smirnov, Nikita; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Joshua Wyatt; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snyder, Ian Michael; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Søgaard, Andreas; Soh, Dart-yin; Sokhrannyi, Grygorii; Solans Sanchez, Carlos; Solar, Michael; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Son, Hyungsuk; Sopczak, Andre; Sosa, David; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spangenberg, Martin; Spanò, Francesco; Sperlich, Dennis; Spettel, Fabian; Spieker, Thomas Malte; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; St Denis, Richard Dante; Stabile, Alberto; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanitzki, Marcel Michael; Stapf, Birgit Sylvia; Stapnes, Steinar; Starchenko, Evgeny; Stark, Giordon; Stark, Jan; Stark, Simon Holm; Staroba, Pavel; Starovoitov, Pavel; Stärz, Steffen; Staszewski, Rafal; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stewart, Graeme; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Suchek, Stanislav; Sugaya, Yorihito; Suk, Michal; Sulin, Vladimir; Sultan, D M S; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Suruliz, Kerim; Suster, Carl; Sutton, Mark; Suzuki, Shota; Svatos, Michal; Swiatlowski, Maximilian; Swift, Stewart Patrick; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takasugi, Eric Hayato; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tanaka, Junichi; Tanaka, Masahiro; Tanaka, Reisaburo; Tanaka, Shuji; Tanioka, Ryo; Tannenwald, Benjamin Bordy; Tapia Araya, Sebastian; Tapprogge, Stefan; Tarem, Shlomit; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Aaron; Taylor, Geoffrey; Taylor, Pierre Thor Elliot; Taylor, Wendy; Teixeira-Dias, Pedro; Temple, Darren; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Paul; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tisserant, Sylvain; Todome, Kazuki; Todorova-Nova, Sharka; Todt, Stefanie; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tong, Baojia(Tony); Tornambe, Peter; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Treado, Colleen Jennifer; Trefzger, Thomas; Tresoldi, Fabio; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Trofymov, Artur; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsang, Ka Wa; Tseng, Jeffrey; Tsiareshka, Pavel; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsui, Ka Ming; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tu, Yanjun; Tudorache, Alexandra; Tudorache, Valentina; Tulbure, Traian Tiberiu; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turgeman, Daniel; Turk Cakir, Ilkay; Turra, Ruggero; Tuts, Michael; Ucchielli, Giulia; Ueda, Ikuo; Ughetto, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usui, Junya; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vaidya, Amal; Valderanis, Chrysostomos; Valdes Santurio, Eduardo; Valentinetti, Sara; Valero, Alberto; Valéry, Lo\\"ic; Valkar, Stefan; Vallier, Alexis; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; van der Graaf, Harry; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varni, Carlo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vasquez, Jared Gregory; Vasquez, Gerardo; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veeraraghavan, Venkatesh; Veloce, Laurelle Maria; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Ambrosius Thomas; Vermeulen, Jos; Vetterli, Michel; Viaux Maira, Nicolas; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigani, Luigi; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vishwakarma, Akanksha; Vittori, Camilla; Vivarelli, Iacopo; Vlachos, Sotirios; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; von der Schmitt, Hans; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Peter; Wagner, Wolfgang; Wagner-Kuhr, Jeannine; Wahlberg, Hernan; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wallangen, Veronica; Wang, Chao; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Qing; Wang, Rui; Wang, Song-Ming; Wang, Tingting; Wang, Wei; Wang, Wenxiao; Wang, Zirui; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Watkins, Peter; Watson, Alan; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Aaron Foley; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Weber, Stephen; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weirich, Marcel; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Michael David; Werner, Per; Wessels, Martin; Whalen, Kathleen; Whallon, Nikola Lazar; Wharton, Andrew Mark; White, Aaron; White, Andrew; White, Martin; White, Ryan; Whiteson, Daniel; Whitmore, Ben William; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilk, Fabian; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, John; Wingerter-Seez, Isabelle; Winkels, Emma; Winklmeier, Frank; Winston, Oliver James; Winter, Benedict Tobias; Wittgen, Matthias; Wobisch, Markus; Wolf, Tim Michael Heinz; Wolff, Robert; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Vincent Wai Sum; Worm, Steven; Wosiek, Barbara; Wotschack, Jorg; Wozniak, Krzysztof; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xi, Zhaoxu; Xia, Ligang; Xu, Da; Xu, Lailin; Xu, Tairan; Yabsley, Bruce; Yacoob, Sahal; Yamaguchi, Daiki; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamatani, Masahiro; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yang, Zongchang; Yao, Weiming; Yap, Yee Chinn; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yigitbasi, Efe; Yildirim, Eda; Yorita, Kohei; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Yu, Jaehoon; Yu, Jie; Yuen, Stephanie P; Yusuff, Imran; Zabinski, Bartlomiej; Zacharis, Georgios; Zaidan, Remi; Zaitsev, Alexander; Zakharchuk, Nataliia; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanzi, Daniele; Zeitnitz, Christian; Zemaityte, Gabija; Zemla, Andrzej; Zeng, Jian Cong; Zeng, Qi; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Guangyi; Zhang, Huijun; Zhang, Jinlong; Zhang, Lei; Zhang, Liqing; Zhang, Matt; Zhang, Peng; Zhang, Rui; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Yu; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhou, Bing; Zhou, Chen; Zhou, Li; Zhou, Maosen; Zhou, Mingliang; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; Zou, Rui; zur Nedden, Martin; Zwalinski, Lukasz

    2017-09-19

    A search for new phenomena in final states characterized by high jet multiplicity, an isolated lepton (electron or muon) and either zero or at least three b-tagged jets is presented. The search uses 36.1 fb$^{-1}$ of $\\sqrt{s}$ = 13 TeV proton-proton collision data collected by the ATLAS experiment at the Large Hadron Collider in 2015 and 2016. The dominant sources of background are estimated using parameterized extrapolations, based on observables at medium jet multiplicity, to predict the b-tagged jet multiplicity distribution at the higher jet multiplicities used in the search. No significant excess over the Standard Model expectation is observed and 95% confidence-level limits are extracted constraining four simplified models of R-parity-violating supersymmetry that feature either gluino or top-squark pair production. The exclusion limits reach as high as 2.1 TeV in gluino mass and 1.2 TeV in top-squark mass in the models considered. In addition, an upper limit is set on the cross-section for Standar...

  3. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  4. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  5. Multiple mononeuropathy

    Science.gov (United States)

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  6. Calculation methodology validation. Pt. 2/01-R. Calculation of the multiplication factor for eight experiments with a critical set of nineteen VVER-440 fuel assemblies

    International Nuclear Information System (INIS)

    Kyncl, J.

    2001-04-01

    Comparison calculations were performed for 8 experiments accomplished in 2000 on the LR-0 reactor. The MCNP4a code was applied using effective cross section data in the continuous representation as per the ENDF/B-VI library. (P.A.)

  7. Over-expression of bacterial gamma-glutamylcysteine synthetase (GSH1) in plastids affects photosynthesis, growth and sulphur metabolism in poplar (Populus tremula x Populus alba) dependent on the resulting gamma-glutamylcysteine and glutathione levels.

    Science.gov (United States)

    Herschbach, Cornelia; Rizzini, Luca; Mult, Susanne; Hartmann, Tanja; Busch, Florian; Peuke, Andreas D; Kopriva, Stanislav; Ensminger, Ingo

    2010-07-01

    We compared three transgenic poplar lines over-expressing the bacterial gamma-glutamylcysteine synthetase (GSH1) targeted to plastids. Lines Lggs6 and Lggs12 have two copies, while line Lggs20 has three copies of the transgene. The three lines differ in their expression levels of the transgene and in the accumulation of gamma-glutamylcysteine (gamma-EC) and glutathione (GSH) in leaves, roots and phloem exudates. The lowest transgene expression level was observed in line Lggs6 which showed an increased growth, an enhanced rate of photosynthesis and a decreased excitation pressure (1-qP). The latter typically represents a lower reduction state of the plastoquinone pool, and thereby facilitates electron flow along the electron transport chain. Line Lggs12 showed the highest transgene expression level, highest gamma-EC accumulation in leaves and highest GSH enrichment in phloem exudates and roots. This line also exhibited a reduced growth, and after a prolonged growth of 4.5 months, symptoms of leaf injury. Decreased maximum quantum yield (F(v)/F(m)) indicated down-regulation of photosystem II reaction centre (PSII RC), which correlates with decreased PSII RC protein D1 (PsbA) and diminished light-harvesting complex (Lhcb1). Potential effects of changes in chloroplastic and cytosolic GSH contents on photosynthesis, growth and the whole-plant sulphur nutrition are discussed for each line.

  8. Over-expression and siRNA of a novel environmental lipopolysaccharide-responding gene on the cell cycle of the human hepatoma-derived cell line HepG2

    International Nuclear Information System (INIS)

    Du Kejun; Chai Yubo; Hou Lichao; Chang Wenhui; Chen Suming; Luo Wenjing; Cai Tongjian; Zhang Xiaonan; Chen Nanchun; Chen Yaoming; Chen Jingyuan

    2008-01-01

    Lipopolysaccharide (LPS) is the toxic determinant for Gram-negative bacterium infection. The individual response to LPS was related to its gene background. It is necessary to identify new molecules and signaling transduction pathways about LPS. The present study was undertaken to evaluate the effects of a novel environmental lipopolysaccharide-responding (Elrg) gene on the regulation of proliferation and cell cycle of the hepatoma-derived cell line, HepG2. By means of RT-PCR, the new molecule of Elrg was generated from a human dental pulp cell cDNA library. Expression level of Elrg in HepG2 cells was remarkably upgraded by the irritation of LPS. Localization of Elrg in HepG2 cells was positioned mainly in cytoplasm. HepG2 cells were markedly arrested in the G1 phase by over-expressing Elrg. The percentage of HepG2 cells in G1 phase partly decreased after Elrg-siRNA. In conclusion, Elrg is probably correlative with LPS responding. Elrg is probably a new protein in cytoplasm which plays an important role in regulating cell cycle. The results will deepen our understanding about the potential effects of Elrg on the human hepatoma-derived cell line HepG2

  9. Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas

    Directory of Open Access Journals (Sweden)

    Katerina Vrzalikova

    2012-10-01

    Full Text Available B-lymphocyte-induced maturation protein 1 (BLIMP1 exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC B cell differentiation. In contrast, the shorter β isoform is functionally impaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL. We have studied the influence on BLIMP1β expression of the Epstein-Barr virus (EBV, a human herpesvirus that is implicated in the pathogenesis of several GC-derived lymphomas, including a subset of DLBCL and Hodgkin’s lymphoma (HL. We show that BLIMP1β expression is increased following the EBV infection of normal human tonsillar GC B cells. We also show that this change in expression is accompanied by hypomethylation of the BLIMP1β-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1β promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1β is hypomethylated in the Hodgkin/Reed-Sternberg (HRS cells of HL. Our results provide evidence in support of a role for BLIMP1β in the pathogenesis of EBV-associated B cell lymphomas.

  10. Neutron source multiplication method

    International Nuclear Information System (INIS)

    Clayton, E.D.

    1985-01-01

    Extensive use has been made of neutron source multiplication in thousands of measurements of critical masses and configurations and in subcritical neutron-multiplication measurements in situ that provide data for criticality prevention and control in nuclear materials operations. There is continuing interest in developing reliable methods for monitoring the reactivity, or k/sub eff/, of plant operations, but the required measurements are difficult to carry out and interpret on the far subcritical configurations usually encountered. The relationship between neutron multiplication and reactivity is briefly discussed and data presented to illustrate problems associated with the absolute measurement of neutron multiplication and reactivity in subcritical systems. A number of curves of inverse multiplication have been selected from a variety of experiments showing variations observed in multiplication during the course of critical and subcritical experiments where different methods of reactivity addition were used, with different neutron source detector position locations. Concern is raised regarding the meaning and interpretation of k/sub eff/ as might be measured in a far subcritical system because of the modal effects and spectrum differences that exist between the subcritical and critical systems. Because of this, the calculation of k/sub eff/ identical with unity for the critical assembly, although necessary, may not be sufficient to assure safety margins in calculations pertaining to far subcritical systems. Further study is needed on the interpretation and meaning of k/sub eff/ in the far subcritical system

  11. Application and analysis of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for patients with multiple renal tumor: initial experience.

    Science.gov (United States)

    Zhu, Jundong; Jiang, Fan; Li, Pu; Shao, Pengfei; Liang, Chao; Xu, Aiming; Miao, Chenkui; Qin, Chao; Wang, Zengjun; Yin, Changjun

    2017-09-11

    To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline. For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

  12. Strategies that facilitate participation in family activities of children and adolescents with profound intellectual and multiple disabilities: parents' and personal assistants' experiences.

    Science.gov (United States)

    Axelsson, Anna Karin; Imms, Christine; Wilder, Jenny

    2014-01-01

    Participation throughout one's life plays a significant role for development and emotional well-being. For this reason, there is a need to identify ways to facilitate participation in family activities for children and adolescents with profound intellectual and multiple disabilities (PIMD). The study design was qualitative and explorative, based on semi structured interviews with 11 parents and 9 personal assistants of children with PIMD. The interviews revealed participation-facilitating strategies relating to the children's/adolescent's proximal environment, such as "Availability and acceptability of the activity", "Good knowledge about the child" and a "A positive attitude of people close to the child", as well as strategies related to the children/adolescents themselves: "Sense of belonging", "Possible for the child/adolescent to understand", "Opportunities to influence" and "Feeling of being needed". Children and adolescents with PIMD are dependent on support obtained through their environment. The identified strategies, individually adapted through awareness and knowledge by the parents and the personal assistants, provide important evidence to assist our understanding in gaining understanding about how to improve participation in family activities of children and adolescents with PIMD. Participation-facilitating strategies related to the child/adolescent and his or her proximal environments are identified to improve participation in children and adolescents with profound intellectual and multiple disabilities (PIMD). Examples of strategies for the child's/adolescents' proximal environment include "good knowledge about the child/adolescent", and, for the child/adolescent, include creating "sense of belonging" and "opportunities to influence". Identifying and making these strategies explicit may assist in enhancing the participation of children and adolescents with PIMD in family activities. People in the child's/adolescent's proximal environment need to set

  13. The Border Multiple

    DEFF Research Database (Denmark)

    of European borders by looking at border practices in the light of the mobility turn, and thus as dynamic, multiple, diverse and best expressed in everyday experiences of people living at and with borders, rather than focusing on static territorial divisions between states and regions at geopolitical level...

  14. [Multiple meningiomas].

    Science.gov (United States)

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Assessing the potential impact of non-proprietary drug copies on quality of medicine and treatment in patients with relapsing multiple sclerosis: the experience with fingolimod

    Directory of Open Access Journals (Sweden)

    Correale J

    2014-06-01

    Full Text Available Jorge Correale,1 Erwin Chiquete,2 Snezana Milojevic,3 Nadina Frider,3 Imre Bajusz31Raúl Carrea Institute for Neurological Research, Foundation for the Fight against Infant Neurological Illnesses, Buenos Aires, Argentina; 2Department of Neurology and Psychiatry, Salvador Zubirán National Institute of Medical Science and Nutrition, Mexico City, Mexico; 3Novartis Pharma AG, Basel, SwitzerlandBackground: Fingolimod is a once-daily oral treatment for relapsing multiple sclerosis, the proprietary production processes of which are tightly controlled, owing to its susceptibility to contamination by impurities, including genotoxic impurities. Many markets produce nonproprietary medicines; assessing their efficacy and safety is difficult as regulators may approve nonproprietary drugs without bioequivalence data, genotoxic evaluation, or risk management plans (RMPs. This assessment is especially important for fingolimod given its solubility/bioavailability profile, genotoxicity risk, and low-dose final product (0.5 mg. This paper presents an evaluation of the quality of proprietary and nonproprietary fingolimod variants.Methods: Proprietary fingolimod was used as a reference substance against which eleven nonproprietary fingolimod copies were assessed. The microparticle size distribution of each compound was assessed by laser light diffraction, and inorganic impurity content by sulfated ash testing. Heavy metals content was quantified using inductively coupled plasma optical emission spectrometry, and levels of unspecified impurities by high-performance liquid chromatography. Solubility was assessed in a range of solvents at different pH values. Key information from the fingolimod RMP is also presented.Results: Nonproprietary fingolimod variants exhibited properties out of proprietary or internationally accepted specifications, including differences in particle size distribution and levels of impurities such as heavy metals. For microparticle size and

  16. [Extensive cranioplasty for sagittal synostosis in young children by preserving multiple cranial bone flaps adhered to the dura mater: experience with 63 cases].

    Science.gov (United States)

    Bao Nan; Chu Jun; Wang Xue; Yang, Bo; Song, Yunhai; Cai, Jinjing

    2016-01-01

    This study aimed to evaluate the effort of applying frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater in the treatment of sagittal synostosis. From April 2008 to June 2013, sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. The CT images showed that both sides of the parietal bone of artificial sagittal groove gradually merged postoperative 1 year, and skull almost completely normal healing after operation 2 or 3 years, without deformity recurrence within 5 years. Among them all, 61 children's intelligence is normal and 2 children's lagged behind normal level, no further improvement. Patients were followed up 1 - 5 years (an average of 43 months). Skull growth was excellent in all patients, the anteroposterior diameter was shortened by 14.6 mm averagely, the transverse diameter was increased by 12.3 mm averagely, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis. The application of frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater can be used in the treatment of sagittal

  17. Comprehensive ecosystem model-data synthesis using multiple data sets at two temperate forest free-air CO2 enrichment experiments: Model performance at ambient CO2 concentration

    Science.gov (United States)

    Walker, Anthony P.; Hanson, Paul J.; De Kauwe, Martin G.; Medlyn, Belinda E.; Zaehle, Sönke; Asao, Shinichi; Dietze, Michael; Hickler, Thomas; Huntingford, Chris; Iversen, Colleen M.; Jain, Atul; Lomas, Mark; Luo, Yiqi; McCarthy, Heather; Parton, William J.; Prentice, I. Colin; Thornton, Peter E.; Wang, Shusen; Wang, Ying-Ping; Warlind, David; Weng, Ensheng; Warren, Jeffrey M.; Woodward, F. Ian; Oren, Ram; Norby, Richard J.

    2014-05-01

    Free-air CO2 enrichment (FACE) experiments provide a remarkable wealth of data which can be used to evaluate and improve terrestrial ecosystem models (TEMs). In the FACE model-data synthesis project, 11 TEMs were applied to two decadelong FACE experiments in temperate forests of the southeastern U.S.—the evergreen Duke Forest and the deciduous Oak Ridge Forest. In this baseline paper, we demonstrate our approach to model-data synthesis by evaluating the models' ability to reproduce observed net primary productivity (NPP), transpiration, and leaf area index (LAI) in ambient CO2 treatments. Model outputs were compared against observations using a range of goodness-of-fit statistics. Many models simulated annual NPP and transpiration within observed uncertainty. We demonstrate, however, that high goodness-of-fit values do not necessarily indicate a successful model, because simulation accuracy may be achieved through compensating biases in component variables. For example, transpiration accuracy was sometimes achieved with compensating biases in leaf area index and transpiration per unit leaf area. Our approach to model-data synthesis therefore goes beyond goodness-of-fit to investigate the success of alternative representations of component processes. Here we demonstrate this approach by comparing competing model hypotheses determining peak LAI. Of three alternative hypotheses—(1) optimization to maximize carbon export, (2) increasing specific leaf area with canopy depth, and (3) the pipe model—the pipe model produced peak LAI closest to the observations. This example illustrates how data sets from intensive field experiments such as FACE can be used to reduce model uncertainty despite compensating biases by evaluating individual model assumptions.

  18. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  19. Staff and students' perceptions and experiences of teaching and assessment in Clinical Skills Laboratories: interview findings from a multiple case study.

    Science.gov (United States)

    Houghton, Catherine E; Casey, Dympna; Shaw, David; Murphy, Kathy

    2012-08-01

    The Clinical Skills Laboratory has become an essential structure in nurse education and several benefits of its use have been identified. However, the literature identifies the need to examine the transferability of skills learned there into the reality of practice. This research explored the role of the Clinical Skills Laboratory in preparing nursing students for the real world of practice. This paper focuses specifically on the perceptions of the teaching and assessment strategies employed there. Qualitative multiple case study design. Five case study sites. Interviewees (n=58) included academic staff, clinical staff and nursing students. Semi-structured interviews. The Clinical Skills Laboratory can provide a pathway to practice and its authenticity is significant. Teaching strategies need to incorporate communication as well as psychomotor skills. Including audio-visual recording into assessment strategies is beneficial. Effective relationships between education institutions and clinical settings are needed to enhance the transferability of the skills learned. The Clinical Skills Laboratory should provide an authentic learning environment, with the appropriate use of teaching strategies. It is crucial that effective links between educators and clinical staff are established and maintained. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Comparison of the multiple mini-interview with the traditional interview for U.S. emergency medicine residency applicants: a single-institution experience.

    Science.gov (United States)

    Soares, William E; Sohoni, Aparajita; Hern, Herbert G; Wills, Charlotte P; Alter, Harrison J; Simon, Barry C

    2015-01-01

    The multiple mini-interview (MMI) is a validated interview technique used primarily to evaluate medical school applicants. No study has compared MMIs with traditional interviews (TIs) in the evaluation of U.S. emergency medicine residency (EMR) applicants. During the 2011-2012 interview season, a four-station MMI was incorporated into the interview process for EMR applicants at Alameda Health System-Highland Hospital (AHS). A postinterview anonymous questionnaire was offered to all applicants after they submitted their rank lists but prior to release of National Residency Matching Program results. Respondents rated their perceptions of the MMI and TI on a five-point Likert scale. McNemar chi-square test was used to explore differences in respondents' perceptions of interview styles. One hundred ten interviewees completed the survey (73%). Overall, applicants found the TI more enjoyable than the MMI process (98 [89%] compared with 48 [44%], McNemar chi-square=28.66, P<.01) and preferred the TI process to the MMI (66 [60%] compared with 9 [10%], McNemar chi-square=40.81, P<.01). Sixteen applicants (14%) indicated that the use of the MMI would negatively affect their ranking of the program. In contrast to prior studies, U.S. EMR applicants to AHS preferred the TI to the MMI. Further investigation into the use of the MMI for selecting U.S. EMR applicants is warranted.

  1. Evaluation of accuracy of Monte Carlo code MVP with VHTRC experiments. Multiplication factor at criticality, burnable poison worth and void worth

    International Nuclear Information System (INIS)

    Nojiri, Naoki; Yamashita, Kiyonobu; Fiujimoto, Nozomu; Nakano, Masaaki , Yamane, Tsuyoshi; Akino, Fujiyoshi.

    1997-11-01

    Experimental data of VHTRC (Very High Temperature Reactor Critical Assembly) were analyzed using Monte Carlo code MVP (general purpose Monte Carlo code of neutron and photon transport calculations based on the continuous energy method). The calculation accuracy of the code was evaluated by the analysis for nuclear characteristics of a HTGR (high temperature gas-cooled reactor). The MVP code can analyze with a detailed three-dimensional core model with a few approximations. The HTGRs have following characteristics from view point of nuclear design : they have burnable poisons, many void holes, namely, the control insertion holes and so on. Taking account of these characteristics, multiplication factor at criticality, burnable poison worth, and void worth were evaluated. The maximum calculation errors were 0.8%Δk, 7%, and 25% respectively, From these results, it can be concluded that the MVP code is able to be applied to the nuclear characteristics analysis of the HTGR like the High Temperature Engineering Test Reactor (HTTR). (author)

  2. Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

    Science.gov (United States)

    Casamento, K; Laverty, A; Wilsher, M; Twiss, J; Gabbay, E; Glaspole, I; Jaffe, A

    2016-04-18

    We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.

  3. iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway

    International Nuclear Information System (INIS)

    Chen, Jinfeng; Xie, Fei; Zhang, Lijian; Jiang, Wen G

    2010-01-01

    iASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. The present study investigated the expression of iASPP in clinical lung cancer, a leading cancer type in the world, and the biological impact of this molecule on lung cancer cells. iASPP protein levels in lung cancer tissues were evaluated using an immunohistochemical method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated shRNA method and the biological impact after knocking down iASSP on lung cancer cell lines was investigated in connection with the p53 expression status. We showed here that the expression of iASPP was significantly higher in lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA treatment resulted in a down-regulation of iASPP in lung cancer cells. There was a subsequent reduction of cell proliferation of the two lung tumour cell lines A459 and 95D both of which had wild-type p53 expression. In contrast, reduction of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its growth rate. iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway. Together with the pattern of the over-expression in clinical lung cancers, it is concluded that iASPP plays an pivotal role in the progression of lung cancer and is a potential target for lung cancer therapy

  4. Interaction between amiodarone and hepatitis-C virus nucleotide inhibitors in human induced pluripotent stem cell-derived cardiomyocytes and HEK-293 Cav1.2 over-expressing cells.

    Science.gov (United States)

    Lagrutta, Armando; Zeng, Haoyu; Imredy, John; Balasubramanian, Bharathi; Dech, Spencer; Lis, Edward; Wang, Jixin; Zhai, Jin; DeGeorge, Joseph; Sannajust, Frederick

    2016-10-01

    Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases. AMIO co-applied with SOF or MNI-1 increased beating rate or field potential (FP) rate and decreased impedance (IMP) and Ca(2+) transient amplitudes in hiPSC-CM syncytia. This action resembled that of Ca(2+) channel blockers (CCBs) in the model, but CCBs did not substitute for AMIO in the DDI. AMIO analog dronedarone (DRON) did not substitute for, but competed with AMIO in the DDI. Ryanodine and thapsigargin, decreasing intracellular Ca(2+) stores, and SEA-0400, a Na(+)/Ca(2+) exchanger-1 (NCX1) inhibitor, partially antagonized or suppressed DDI effects. Other agents affecting FP rate only exerted additive or subtractive effects, commensurate with their individual effects. We also describe an interaction between AMIO and MNI-1 on Cav1.2 ion channels in an over-expressing HEK-293 cell line. MNI-1 enhanced Cav1.2 channel inhibition by AMIO, but did not affect inhibition of Cav1.2 by DRON, verapamil, nifedipine, or diltiazem. Our data in hiPSC-CMs indicate that HCV-NI agents such as SOF and MNI-1 interact with key intracellular Ca(2+)-handling mechanisms. Additional study in a Cav1.2 HEK-293 cell-line suggests that HCV-NIs potentiate the inhibitory action of AMIO on L-type Ca(2+) channels. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Characterization of Rice Homeobox Genes, OsHOX22 and OsHOX24, and Over-expression of OsHOX24 in Transgenic Arabidopsis Suggest their Role in Abiotic Stress Response

    Directory of Open Access Journals (Sweden)

    Annapurna eBhattacharjee

    2016-05-01

    Full Text Available Homeobox transcription factors are well known regulators of plant growth and development. In this study, we carried out functional analysis of two candidate stress-responsive HD-ZIP I class homeobox genes from rice, OsHOX22 and OsHOX24. These genes were highly upregulated under various abiotic stress conditions at different stages of rice development, including seedling, mature and reproductive stages. The transcript levels of these genes were enhanced significantly in the presence of plant hormones, including abscisic acid (ABA, auxin, salicylic acid and gibberellic acid. The recombinant full-length and truncated homeobox proteins were found to be localized in the nucleus. Electrophoretic mobility shift assay established the binding of these homeobox proteins with specific DNA sequences, AH1 (CAAT(A/TATTG and AH2 (CAAT(C/GATTG. Transactivation assays in yeast revealed the transcriptional activation potential of full-length OsHOX22 and OsHOX24 proteins. Homo- and hetero-dimerization capabilities of these proteins have also been demonstrated. Further, we identified putative novel interacting proteins of OsHOX22 and OsHOX24 via yeast-two hybrid analysis. Over-expression of OsHOX24 imparted higher sensitivity to stress hormone, ABA, and abiotic stresses in the transgenic Arabidopsis plants as revealed by various physiological and phenotypic assays. Microarray analysis revealed differential expression of several stress-responsive genes in transgenic lines as compared to wild-type. Many of these genes were found to be involved in transcriptional regulation and various metabolic pathways. Altogether, our results suggest the possible role of OsHOX22/OsHOX24 homeobox proteins as negative regulators in abiotic stress responses.

  6. Multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  7. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  8. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  9. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  10. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  11. Multiple Sclerosis.

    Science.gov (United States)

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  12. Parenting Multiples

    Science.gov (United States)

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  13. Lack of survival improvement with novel anti-myeloma agents for patients with multiple myeloma and central nervous system involvement: the Greek Myeloma Study Group experience.

    Science.gov (United States)

    Katodritou, Eirini; Terpos, Evangelos; Kastritis, Efstathios; Delimpasis, Sossana; Symeonidis, Argiris S; Repousis, Panagiotis; Kyrtsonis, Marie-Christine; Vadikolia, Chrysa; Michalis, Eurydiki; Polychronidou, Genovefa; Michael, Michael; Papadaki, Sofia; Papathanasiou, Maria; Kokoviadou, Kyriaki; Kioumi, Anna; Vlachaki, Eythimia; Hadjiaggelidou, Christina; Kouraklis, Alexandra; Patsias, Ioannis; Gavriatopoulou, Maria; Kotsopoulou, Maria; Verrou, Evgenia; Gastari, Vasiliki; Christoulas, Dimitrios; Giannopoulou, Evlambia; Pouli, Anastasia; Konstantinidou, Pavlina; Anagnostopoulos, Achilles; Dimopoulos, Meletios-Athanasios

    2015-12-01

    Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.

  14. Adaptive introductions: How multiple experiments and comparisons to wild populations provide insights into requirements for long-term introduction success of an endangered shrub

    Directory of Open Access Journals (Sweden)

    Eric S. Menges

    2016-10-01

    Full Text Available Recovery of an imperiled plant species may require augmentation of existing populations or creation of new ones. Hundreds of such projects have been conducted over the last few decades, but there is a bias in the literature favoring successes over failures. In this paper, we evaluate a series of introductions that experimentally manipulated microhabitat and fire in an adaptive introduction framework. Between 2002 and 2012, we (and our collaborators carried out ten introductions and augmentations of Florida ziziphus Pseudoziziphus (Condalia, Ziziphus celata, a clonal shrub limited to very small populations and narrowly endemic to pyrogenic central Florida sandhills. Six of the introductions were designed as experiments to test hypotheses about how demographic performance was affected by microhabitat, fire, and propagule type. Introduced transplants had high survival (<90% annually, inconsistent growth, and little transition to reproduction, while introduced seeds had low germination and survival. Transplants were more efficient than seeds as translocation propagules. Shaded (vs. open sites supported generally higher transplant and seedling survival and seed germination percentages, but growth responses varied among experiments. Supplemental irrigation increased transplant survival and seed germination, but otherwise seedling and plant survival and growth were not significantly affected. Contrary to expectations based on wild populations, introduced propagules have not been more successful in unshaded sites, suggesting that Florida ziziphus has broader microhabitat preferences than hypothesized. Compared to wild plants, introduced plants had similar survival and responses to fire, slower growth, and more delayed flowering. Introduced plants had no clonal spread. While no introduced population has demonstrated a capacity for long-term viability, one augmented population has flowered and produced viable fruits. Given that Florida ziziphus genets are

  15. Delivering HIV care in challenging operating environments: the MSF experience towards differentiated models of care for settings with multiple basic health care needs.

    Science.gov (United States)

    Ssonko, Charles; Gonzalez, Lucia; Mesic, Anita; da Fonseca, Marcio Silveira; Achar, Jay; Safar, Nadia; Martin, Beatriz; Wong, Sidney; Casas, Esther C

    2017-07-21

    Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC). A descriptive analysis from CAR, DRC and RoSS programmes reviewing methodology and strategies of HIV care integration between 2010 and 2015 was performed. We describe HIV care models integrated within the provision of general health care and highlight best practices and challenges. Services included provision of general health care, with out-patient care (range between countries 43,343 and 287,163 consultations/year in 2015) and in-patient care (range 1076-16,595 in 2015). By the end of 2015 antiretroviral therapy (ART) initiations reached 12-255 patients/year. A total of 1101 and 1053 patients were on ART in CAR and DRC, respectively. In RoSS 186 patients were on ART when conflict recommenced late in 2013. While ART initiation and monitoring were mostly clinically driven in the early phase of the programmes, DRC implemented CD4 monitoring and progressively HIV viral load (VL) monitoring during study period. Attacks to health care facilities in CAR and RoSS disrupted service provision temporarily. Programmatic challenges include: competing health priorities influencing HIV care and need to integrate within general health services. Differentiated care approaches that support continuity of care in these programmes include simplification of medical protocols, multi-month ART prescriptions, and community strategies such as ART delivery groups, contingency plans and

  16. Adaptive introductions: How multiple experiments and comparisons to wild populations provide insights into requirements for long-term introduction success of an endangered shrub

    Institute of Scientific and Technical Information of China (English)

    Eric S.Menges; Stacy A.Smith; Carl W.Weekley

    2016-01-01

    Recovery of an imperiled plant species may require augmentation of existing populations or creation of new ones.Hundreds of such projects have been conducted over the last few decades,but there is a bias in the literature favoring successes over failures.In this paper,we evaluate a series of introductions that experimentally manipulated microhabitat and fire in an adaptive introduction framework.Between 2002 and 2012,we (and our collaborators) carried out ten introductions and augmentations of Florida ziziphus Pseudoziziphus (Condalia,Ziziphus) celata,a clonal shrub limited to very small populations and narrowly endemic to pyrogenic central Florida sandhills.Six of the introductions were designed as experiments to test hypotheses about how demographic performance was affected by microhabitat,fire,and propagule type.Introduced transplants had high survival (<90% annually),inconsistent growth,and little transition to reproduction,while introduced seeds had low germination and survival.Transplants were more efficient than seeds as translocation propagules.Shaded (vs.open) sites supported generally higher transplant and seedling survival and seed germination percentages,but growth responses varied among experiments.Supplemental irrigation increased transplant survival and seed germination,but otherwise seedling and plant survival and growth were not significantly affected.Contrary to expectations based on wild populations,introduced propagules have not been more successful in unshaded sites,suggesting that Florida ziziphus has broader microhabitat preferences than hypothesized.Compared to wild plants,introduced plants had similar survival and responses to fire,slower growth,and more delayed flowering.Introduced plants had no clonal spread.While no introduced population has demonstrated a capacity for long-term viability,one augmented population has flowered and produced viable fruits.Given that Florida ziziphus genets are long-lived,low levels of sexual

  17. Unifying Pore Network Modeling, Continuous Time Random Walk (CTRW) Theory and Experiment to Describe Impact of Spatial Heterogeneities on Solute Dispersion at Multiple Length-scales

    Science.gov (United States)

    Bijeljic, B.; Blunt, M. J.; Rhodes, M. E.

    2009-04-01

    This talk will describe and highlight the advantages offered by a novel methodology that unifies pore network modeling, CTRW theory and experiment in description of solute dispersion in porous media. Solute transport in a porous medium is characterized by the interplay of advection and diffusion (described by Peclet number, Pe) that cause dispersion of solute particles. Dispersion is traditionally described by dispersion coefficients, D, that are commonly calculated from the spatial moments of the plume. Using a pore-scale network model based on particle tracking, the rich Peclet-number dependence of dispersion coefficient is predicted from first principles and is shown to compare well with experimental data for restricted diffusion, transition, power-law and mechanical dispersion regimes in the asymptotic limit. In the asymptotic limit D is constant and can be used in an averaged advection-dispersion equation. However, it is highly important to recognize that, until the velocity field is fully sampled, the particle transport is non-Gaussian and D possesses temporal or spatial variation. Furthermore, temporal probability density functions (PDF) of tracer particles are studied in pore networks and an excellent agreement for the spectrum of transition times for particles from pore to pore is obtained between network model results and CTRW theory. Based on the truncated power-law interpretation of PDF-s, the physical origin of the power-law scaling of dispersion coefficient vs. Peclet number has been explained for unconsolidated porous media, sands and a number of sandstones, arriving at the same conclusion from numerical network modelling, analytic CTRW theory and experiment. The length traveled by solute plumes before Gaussian behaviour is reached increases with an increase in heterogeneity and/or Pe. This opens up the question on the nature of dispersion in natural systems where the heterogeneities at the larger scales will significantly increase the range of

  18. Cancer-related information needs and treatment decision-making experiences of people with dementia in England: a multiple perspective qualitative study.

    Science.gov (United States)

    McWilliams, Lorna; Farrell, Carole; Keady, John; Swarbrick, Caroline; Burgess, Lorraine; Grande, Gunn; Bellhouse, Sarah; Yorke, Janelle

    2018-04-12

    Little is known about the cancer experience and support needs of people with dementia. In particular, no evidence currently exists to demonstrate the likely complex decision-making processes for this patient group and the oncology healthcare professionals (HCP) involved in their care. The aim of this study was to explore the cancer-related information needs and decision-making experiences of patients with cancer and comorbid dementia, their informal caregivers and oncology HCPs. Cross-sectional qualitative study. Semistructured interviews were conducted face to face with participants. Interviews were audio recorded and transcribed prior to thematic analysis. Patients with a diagnosis of cancer and dementia, their informal caregivers and oncology HCPs involved in their care, all recruited from a regional treatment cancer centre. Purposeful sample of 10 patients with a diagnosis of cancer-dementia, informal caregivers (n=9) and oncology HCPs (n=12). Four themes were identified: (1) leading to the initial consultation-HCPs require more detailed information on the functional impact of dementia and how it may influence cancer treatment options prior to meeting the patient; (2) communicating clinically relevant information-informal caregivers are relied on to provide patient information, advocate for the patient and support decision-making; (3) adjustments to cancer care-patients with dementia get through treatment with the help of their family and (4) following completion of cancer treatment-there are continuing information needs. Oncology HCPs discussed their need to consult specialists in dementia care to support treatment decision-making. Although patients with cancer-dementia are involved in their treatment decision-making, informal caregivers are generally crucial in supporting this process. Individual patient needs and circumstances related to their cancer must be considered in the context of dementia prognosis highlighting complexities of decision-making in this

  19. Soil erosion transport through multiple rainfall events in the presence of stone cover: Laboratory flume experiments and analysis with the Hairsine-Rose model

    Science.gov (United States)

    Jomaa, S.; Barry, D. A.; Brovelli, A.; Heng, B. P.; Sander, G. C.; Parlange, J.

    2011-12-01

    Soil erosion is a major environmental problem that can lead to loss of fertility and degradation of agricultural fields. In order to develop efficient strategies to mitigate the impact of precipitation and reduce the erosion rate, a process-based understanding of the mechanisms that govern sediment transport and delivery is necessary. Soil state and physical properties prior to a precipitation event can affect significantly the erosion rate. Among the most important soil variables are moisture content, compaction and infiltration capacity. Additionally, the presence of stones on the topsoil surface retards the overland flow discharge, reduces runoff generation as well as the sediment delivery and prevents the development of a surface seal, which in turn maintains the infiltration rate. The aim of this study was to examine in detail the effect of surface stones, soil compaction and sealing for a sequence of rainfall events on soil erosion. Experiments were conducted using the EPFL erosion flume, which was divided into two identical flumes (one with stone and one without). The experiment involved four rainfall events with the precipitation rates: 28, 74, 74 and 28 mm h-1. After each 2-h event, the soil was allowed to air dry for 22 h. The total sediment concentration, the concentration of seven sediment size classes and the flow discharge were measured during each event at the outlet of each flume. Experimental results were analyzed using the Hairsine and Rose (H-R) soil erosion model. Results showed that (i) within each precipitation event, the proportion of each size class for the bare/stone-covered flume pairs at steady state were similar, whereas the initial response differed significantly; (ii) in all cases the effluent was enriched in finer particles relative to the original soil; and (iii) the effluent sediment composition was different from that of the original soil, and there was no clear trend towards the parent soil sediment size composition with time. The

  20. Analysis of shipboard aerosol optical thickness measurements from multiple sunphotometers aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment - Asia

    International Nuclear Information System (INIS)

    Miller, Mark A.; Knobelspiesse, Kirk; Frouin, Robert; Bartholomew, Mary Jane; Reynolds, R. Michael; Pietras, Christophe; Fargion, Giulietta; Quinn, Patricia; Thieuleux, Francois

    2005-01-01

    Marine sunphotometer measurements collected aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment - Asia (ACE-Asia) are used to evaluate the ability of complementary instrumentation to obtain the best possible estimates of aerosol optical thickness and Angstrom exponent from ships at sea. A wide range of aerosol conditions, including clean maritime conditions and highly polluted coastal environments, were encountered during the ACE-Asia cruise. The results of this study suggest that shipboard hand-held sunphotometers and fast-rotating shadow-band radiometers (FRSRs) yield similar measurements and uncertainties if proper measurement protocols are used and if the instruments are properly calibrated. The automated FRSR has significantly better temporal resolution (2 min) than the hand-held sunphotometers when standard measurement protocols are used, so it more faithfully represents the variability of the local aerosol structure in polluted regions. Conversely, results suggest that the hand-held sunphotometers may perform better in clean, maritime air masses for unknown reasons. Results also show that the statistical distribution of the Angstrom exponent measurements is different when the distributions from hand-held sunphotometers are compared with those from the FRSR and that the differences may arise from a combination of factors

  1. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  2. Multiple Strokes

    Directory of Open Access Journals (Sweden)

    Obododimma Oha

    2008-12-01

    Full Text Available This poem playfully addresses the slippery nature of linguistic signification, employing humour and sarcasm in presenting a wide range of human experience. It ironical twists -- and "strokes" (read ambiguously as both a giving a punishment and erotic pleasuring -- move from the naming of location through international discourse of capital to the crumbling relationships between nation states. It reading of the signs of language is tied to the unease and fracture in cultural and political experience.

  3. Experience with multiple control groups in a large population-based case-control study on genetic and environmental risk factors.

    Science.gov (United States)

    Pomp, E R; Van Stralen, K J; Le Cessie, S; Vandenbroucke, J P; Rosendaal, F R; Doggen, C J M

    2010-07-01

    We discuss the analytic and practical considerations in a large case-control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.

  4. Interaction between amiodarone and hepatitis-C virus nucleotide inhibitors in human induced pluripotent stem cell-derived cardiomyocytes and HEK-293 Cav{sub 1.2} over-expressing cells

    Energy Technology Data Exchange (ETDEWEB)

    Lagrutta, Armando, E-mail: armando_lagrutta@merck.com; Zeng, Haoyu; Imredy, John; Balasubramanian, Bharathi; Dech, Spencer; Lis, Edward; Wang, Jixin; Zhai, Jin; DeGeorge, Joseph; Sannajust, Frederick

    2016-10-01

    Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases. AMIO co-applied with SOF or MNI-1 increased beating rate or field potential (FP) rate and decreased impedance (IMP) and Ca{sup 2+} transient amplitudes in hiPSC-CM syncytia. This action resembled that of Ca{sup 2+} channel blockers (CCBs) in the model, but CCBs did not substitute for AMIO in the DDI. AMIO analog dronedarone (DRON) did not substitute for, but competed with AMIO in the DDI. Ryanodine and thapsigargin, decreasing intracellular Ca{sup 2+} stores, and SEA-0400, a Na{sup +}/Ca{sup 2+} exchanger-1 (NCX1) inhibitor, partially antagonized or suppressed DDI effects. Other agents affecting FP rate only exerted additive or subtractive effects, commensurate with their individual effects. We also describe an interaction between AMIO and MNI-1 on Cav{sub 1.2} ion channels in an over-expressing HEK-293 cell line. MNI-1 enhanced Cav{sub 1.2} channel inhibition by AMIO, but did not affect inhibition of Cav{sub 1.2} by DRON, verapamil, nifedipine, or diltiazem. Our data in hiPSC-CMs indicate that HCV-NI agents such as SOF and MNI-1 interact with key intracellular Ca{sup 2+}-handling mechanisms. Additional study in a Cav{sub 1.2} HEK-293 cell-line suggests that HCV-NIs potentiate the inhibitory action of AMIO on L-type Ca{sup 2+} channels. - Highlights: • Adverse clinical interaction between amiodarone and HCV-NI drugs is captured by in vitro models. • Human iPSC-derived cardiomyocyte

  5. Evaluating water deficit and glyphosate treatment on the accumulation of phenolic compounds and photosynthesis rate in transgenic Codonopsis lanceolata (Siebold & Zucc.) Trautv. over-expressing γ-tocopherol methyltransferase (γ-tmt) gene.

    Science.gov (United States)

    Ghimire, Bimal Kumar; Son, Na-Young; Kim, Seung-Hyun; Yu, Chang Yeon; Chung, Ill-Min

    2017-07-01

    The effect of water stress and herbicide treatment on the phenolic compound concentration and photosynthesis rate in transgenic Codonopsis lanceolata plants over-expressing the γ-tmt gene was investigated and compared to that in control non-transgenic C. lanceolata plants. The total phenolic compound content was investigated using high-performance liquid chromatography combined with diode array detection in C. lanceolata seedlings 3 weeks after water stress and treatment with glyphosate. Changes in the composition of phenolic compounds were observed in leaf and root extracts from transformed C. lanceolata plants following water stress and treatment with glyphosate. The total concentration of phenolic compounds in the leaf extracts of transgenic samples after water stress ranged from 3455.13 ± 40.48 to 8695.00 ± 45.44 µg g -1 dry weight (DW), whereas the total concentration phenolic compound in the leaf extracts of non-transgenic control samples was 5630.83 ± 45.91 µg g -1  DW. The predominant phenolic compounds that increased after the water stress in the transgenic leaf were (+) catechin, benzoic acid, chlorogenic acid, ferulic acid, gallic acid, rutin, vanillic acid, and veratric acid. The total concentration of phenolic compounds in the leaf extracts of transgenic samples after glyphosate treatment ranged from 4744.37 ± 81.81 to 12,051.02 ± 75.00 µg g -1 DW, whereas the total concentration of the leaf extracts of non-transgenic control samples after glyphosate treatment was 3778.28 ± 59.73 µg g -1 DW. Major phenolic compounds that increased in the transgenic C. lanceolata plants after glyphosate treatment included kaempherol, gallic acid, myricetin, p-hydroxybenzjoic acid, quercetin, salicylic acid, t-cinnamic acid, catechin, benzoicacid, ferulic acid, protocatechuic acid, veratric acid, and vanillic acid. Among these, vanillic acid showed the greatest increase in both leaf and root extracts from transgenic plants relative to

  6. The hepatic Raldh1 expression is elevated in Zucker fatty rats and its over-expression introduced the retinal-induced Srebp-1c expression in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available The roles of vitamin A (VA in the development of metabolic diseases remain unanswered. We have reported that retinoids synergized with insulin to induce the expression of sterol-regulatory element-binding protein 1c gene (Srebp-1c expression in primary rat hepatocytes. Additionally, the hepatic Srebp-1c expression is elevated in Zucker fatty (ZF rats, and reduced in those fed a VA deficient diet. VA is metabolized to retinoic acid (RA for regulating gene expression. We hypothesized that the expression of RA production enzymes contributes to the regulation of the hepatic Srebp-1c expression. Therefore, we analyzed their expression levels in Zucker lean (ZL and ZF rats. The mRNA levels of retinaldehyde dehydrogenase family 1 gene (Raldh1 were found to be higher in the isolated and cultured primary hepatocytes from ZF rats than that from ZL rats. The RALDH1 protein level was elevated in the liver of ZF rats. Retinol and retinal dose- and time-dependently induced the expression of RA responsive Cyp26a1 gene in hepatocytes and hepatoma cells. INS-1 cells were identified as an ideal tool to study the effects of RA production on the regulation of gene expression because only RA, but not retinal, induced Srebp-1c mRNA expression in them. Recombinant adenovirus containing rat Raldh1 cDNA was made and used to infect INS-1 cells. The over-expression of RALDH1 introduced the retinal-mediated induction of Srebp-1c expression in INS-1 cells. We conclude that the expression levels of the enzymes for RA production may contribute to the regulation of RA responsive genes, and determine the responses of the cells to retinoid treatments. The elevated hepatic expression of Raldh1 in ZF rats may cause the excessive RA production from retinol, and in turn, result in higher Srebp-1c expression. This excessive RA production may be one of the factors contributing to the elevated lipogenesis in the liver of ZF rats.

  7. Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the adverse childhood experiences study.

    Science.gov (United States)

    Edwards, Valerie J; Holden, George W; Felitti, Vincent J; Anda, Robert F

    2003-08-01

    childhood maltreatment on adult mental health should include assessments of a wide range of abusive experiences, as well as the family atmosphere in which they occur.

  8. Multiple inflation

    International Nuclear Information System (INIS)

    Murphy, P.J.

    1987-01-01

    The Theory of Inflation, namely, that at some point the entropy content of the universe was greatly increased, has much promise. It may solve the puzzles of homogeneity and the creation of structure. However, no particle physics model has yet been found that can successfully drive inflation. The difficulty in satisfying the constraint that the isotropy of the microwave background places on the effective potential of prospective models is immense. In this work we have codified the requirements of such models in a most general form. We have carefully calculated the amounts of inflation the various problems of the Standard Model need for their solution. We have derived a completely model independent upper bond on the inflationary Hubble parameter. We have developed a general notation with which to probe the possibilities of Multiple Inflation. We have shown that only in very unlikely circumstances will any evidence of an earlier inflation, survive the de Sitter period of its successor. In particular, it is demonstrated that it is most unlikely that two bouts of inflation will yield high amplitudes of density perturbations on small scales and low amplitudes on large. We conclude that, while multiple inflation will be of great theoretical interest, it is unlikely to have any observational impact

  9. Incidence of complications in dermatological surgery of melanoma and non-melanoma skin cancer in patients with multiple comorbidity and/or antiplatelet-anticoagulants. Five year experience in our Hospital.

    Science.gov (United States)

    Arguello-Guerra, Lilia; Vargas-Chandomid, Estefanía; Díaz-González, Jose Manuel; Méndez-Flores, Silvia; Ruelas-Villavicencio, Ana; Domínguez-Cherit, Judith

    2018-01-01

    Surgery is performed more frequently now at days, due to the increasing incidence of melanoma and no-melanoma skin cancer. There are different opinions among dermatologic surgeons between to continue or discontinue antithrombotic therapy prior to the procedure, which increases the risk of thromboembolic events. Prophylaxis with oral antibiotics in the postsurgical period is controversial. To report the safety of surgery without suspending antithrombotic therapy and without oral antibiotic prophylaxis in dermatology surgery of patients with multiple comorbidities and polypharmacy. We designed a retrospective study. We included a total of 655 patients; 96.6% had at least one comorbidity; 27.7% used aspirin and 4.3% some type of antithrombotic therapy. The most common type of skin tumor was basal cell carcinoma with 69.8% . The complication rate was 4.2%; the most was wound dehiscence (1.1%), followed by partial necrosis (0.9%), infection (0.9%), reaction to foreign body (0.6%), complete necrosis (0.3%), bleeding (0.2%) and fistulae (0.2%). Based on the literature and our experience, dermatologic surgery is safe without suspending antithrombotic therapy or antibiotic prophylaxis in patients with multiple comorbidity. Copyright: © 2018 Permanyer.

  10. Additive versus multiplicative muon conservation

    International Nuclear Information System (INIS)

    Nemethy, P.

    1981-01-01

    Experimental elucidation of the question of muon conservation is reviewed. It is shown that neutral-current experiments have not yet yielded information about muonium-antimuonium conversion at the weak-interaction level and that all the charged-current experiments agree that there is no evidence for a multiplicative law. The best limits, from the muon-decay neutrino experiment at LAMPF and from the inverse muon-decay experiment in the CERN neutrino beam, definitely exclude multiplicative law schemes with a branching ratio R approximately 1/2. It is concluded that unless the dynamics conspire to make a multiplicative law with very small R it would appear that muon conservation obeys conserved additive lepton flavor law. (U.K.)

  11. Kir 4.1 inward rectifier potassium channel is upregulated in astrocytes in a murine multiple sclerosis model.

    Science.gov (United States)

    Mercado, Francisco; Almanza, Angélica; Rubio, Nazario; Soto, Enrique

    2018-06-11

    Multiple sclerosis (MS) is a high prevalence degenerative disease characterized at the cellular level by glial and neuronal cell death. The causes of cell death during the disease course are not fully understood. In this work we demonstrate that in a MS model induced by Theiler's murine encephalomyelitis virus (TMEV) infection, the inward rectifier (Kir) 4.1 potassium channel subunit is overexpressed in astrocytes. In voltage clamp experiments the inward current density from TMEV-infected astrocytes was significantly larger than in mock-infected ones. The cRNA hybridization analysis from mock- and TMEV-infected cells showed an upregulation of a potassium transport channel coding sequence. We validated this mRNA increase by RT-PCR and quantitative PCR using Kir 4.1 specific primers. Western blotting experiments confirmed the upregulation of Kir 4.1, and alignment between sequences provided the demonstration that the over-expressed gene encodes for a Kir family member. Flow cytometry showed that the Kir 4.1 protein is located mainly in the cell membrane in mock and TMEV-infected astrocytes. Our results demonstrate an increase in K + inward current in TMEV-infected glial cells, this increment may reduce the neuronal depolarization, contributing to cell resilience mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Dimer of the peptide cycle (Ar-Gly-Asp-D-Phe-Lys) radiolabeled with 99mTc for the integrin s over-expression image: formulation, biokinetics and dosimetry

    International Nuclear Information System (INIS)

    Ortiz A, Z.

    2013-01-01

    In breast cancer, α(v)β(3) and/or α(v)β(5) integrin s are over-expressed in both endothelial and tumour cells. Radiolabeled peptides based on the RGD (Arg-Gly-Asp) sequence are radiopharmaceuticals with high affinity and selectivity for those integrin s. The RGD-dimer peptide (E-[c(RGDfK)] 2 ) radiolabeled with 99m Tc has been reported as a radiopharmaceutical with 10-fold higher affinity for the α(v)β(3) integrin as compared to the RGD-monomer. EDDA (Ethylenediamine-N,N-diacetic acid) is a hydrophilic molecule that may favours renal excretion when used as coligand in the 99m Tc labelling of HYNIC-peptides and can easily be formulated in a lyophilized kit. Aim: Establish a biokinetic model for 99m Tc-EDDA/HYNIC-E-[c(RGDfK)] 2 prepared from lyophilized kits and evaluate the dosimetry as breast cancer imaging agent. Methods: 99m Tc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer ph 7.0 to a lyophilized formulation containing E-[c(RGDfK)] 2 , EDDA, tricine, mannitol and stannous chloride. Radiochemical purity was evaluated by reversed phase HPLC and ITLC-SG analyses. Stability studies in human serum were carried out by size-exclusion HPLC. In-vitro cell uptake was tested using breast cancer cells (MCF7, T47D and MDA-MB-231) with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in MCF7 tumour-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from seven healthy women were acquired at 1, 3, 6 and 24 h after 99m Tc-EDDA/HYNIC-E-[c(RGDfK)] 2 administration obtained with radiochemical purities of >94 %. Regions of interest (ROIs) were drawn around source organs on each time frame. Each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99m Tc-EDDA/HYNIC-E-[c(RGDfK)] 2 time-activity curves in each organ in order to adjust the biokinetic model and to

  13. INDIA: Photon multiplicity detector

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Full text: The team of Indian scientists from Calcutta's Variable Energy Cyclotron Centre, Bhubaneswar Institute of Physics, Panjab (Chandigarh), Rajasthan (Jaipur) and Jammu in collaboration with GSI Darmstadt have contributed a large and highly granular preshower photon multiplicity detector (PMD) for the WA98 experiment at the CERN SPS proton synchrotron. This experiment studies high energy collisions of lead ions and will measure both charged particle and photon multiplicity in a large overlap region. The motivation for measuring photon multiplicity in ultra-relativistic heavy ion collisions stems from theoretical predictions of changes in the relative production of photons and charged particles in the phase transition of hadronic matter to quarkgluon plasma and its subsequent hadronization. The photon multiplicity detector consists of a matrix of scintillator pads placed in light-tight boxes and mounted behind the lead converter plates. The light from the scintillator pads is transported to the readout system using wavelength shifting (WLS) fibres. Developing on the team's earlier experience with a smaller version for the WA93 experiment (September 1991, page 16), several modifications were incorporated to improve light collection and transport. Use of improved WLS fibres, short WLS pieces to minimize self-absorption, and thermal splicing with long clear fibres were some of the important changes incorporated. Tests showed signficantly improved light collection. The scintillator pads were fabricated at all the five collaborating centres in India and the complicated assembly in the detector box modules carried out at the Variable Energy Cyclotron Centre, Calcutta. More than 400 lead converter plates were machined in Calcutta to rigorous tolerances of 0.2 mm. The assembled detector box modules and lead plates were shipped to CERN in spring 1994 for tests and installation. The WA98 PMD consists of over 50,000 scintillator pads of sizes varying from 15 to

  14. INDIA: Photon multiplicity detector

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1995-01-15

    Full text: The team of Indian scientists from Calcutta's Variable Energy Cyclotron Centre, Bhubaneswar Institute of Physics, Panjab (Chandigarh), Rajasthan (Jaipur) and Jammu in collaboration with GSI Darmstadt have contributed a large and highly granular preshower photon multiplicity detector (PMD) for the WA98 experiment at the CERN SPS proton synchrotron. This experiment studies high energy collisions of lead ions and will measure both charged particle and photon multiplicity in a large overlap region. The motivation for measuring photon multiplicity in ultra-relativistic heavy ion collisions stems from theoretical predictions of changes in the relative production of photons and charged particles in the phase transition of hadronic matter to quarkgluon plasma and its subsequent hadronization. The photon multiplicity detector consists of a matrix of scintillator pads placed in light-tight boxes and mounted behind the lead converter plates. The light from the scintillator pads is transported to the readout system using wavelength shifting (WLS) fibres. Developing on the team's earlier experience with a smaller version for the WA93 experiment (September 1991, page 16), several modifications were incorporated to improve light collection and transport. Use of improved WLS fibres, short WLS pieces to minimize self-absorption, and thermal splicing with long clear fibres were some of the important changes incorporated. Tests showed signficantly improved light collection. The scintillator pads were fabricated at all the five collaborating centres in India and the complicated assembly in the detector box modules carried out at the Variable Energy Cyclotron Centre, Calcutta. More than 400 lead converter plates were machined in Calcutta to rigorous tolerances of 0.2 mm. The assembled detector box modules and lead plates were shipped to CERN in spring 1994 for tests and installation. The WA98 PMD consists of over 50,000 scintillator pads of sizes varying from 15 to 25 mm

  15. Sequential and simultaneous multiple explanation

    Directory of Open Access Journals (Sweden)

    Robert Litchfield

    2007-02-01

    Full Text Available This paper reports two experiments comparing variants of multiple explanation applied in the early stages of a judgment task (a case involving employee theft where participants are not given a menu of response options. Because prior research has focused on situations where response options are provided to judges, we identify relevant dependent variables that an intervention might affect when such options are not given. We use these variables to build a causal model of intervention that illustrates both the intended effects of multiple explanation and some potentially competing processes that it may trigger. Although multiple explanation clearly conveys some benefits (e.g., willingness to delay action to engage in information search, increased detail, quality and confidence in alternative explanations in the present experiments, we also found evidence that it may initiate or enhance processes that attenuate its advantages (e.g., feelings that one does not need more data if one has multiple good explanations.

  16. The Border Multiple

    DEFF Research Database (Denmark)

    Addressing and conceptualizing the changing character of borders in contemporary Europe, this book examines developments occurring in the light of European integration processes and an on-going tightening of Europe's external borders. Moreover, the book suggests new ways of investigating the nature...... of European borders by looking at border practices in the light of the mobility turn, and thus as dynamic, multiple, diverse and best expressed in everyday experiences of people living at and with borders, rather than focusing on static territorial divisions between states and regions at geopolitical level...

  17. Multiple Levels of Suffering

    Science.gov (United States)

    Kiley, Kasey B.; Haywood, Carlton; Bediako, Shawn M.; Lanzkron, Sophie; Carroll, C. Patrick; Buenaver, Luis F.; Pejsa, Megan; Edwards, Robert R.; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

    2016-01-01

    Objective: People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. Methods: Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. Results: Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. Discussion: Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology. PMID:26889615

  18. Multiple Input - Multiple Output (MIMO) SAR

    Data.gov (United States)

    National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

  19. A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells

    Directory of Open Access Journals (Sweden)

    Lei Joy X

    2011-01-01

    Full Text Available Abstract Background Molecular changes in multiple biological processes contribute to the development of chronic neurodegeneration such as late onset Alzheimer's disease (LOAD. To discover how these changes are reflected at the level of gene expression, we used a subtractive transcription-based amplification of mRNA procedure to identify novel genes that have altered expression levels in the brains of Alzheimer's disease (AD patients. Among the genes altered in expression level in AD brains was a transcript encoding a novel protein, SDIM1, that contains 146 amino acids, including a typical signal peptide and two transmembrane domains. Here we examined its biochemical properties and putative roles in neuroprotection/neurodegeneration. Results QRT-PCR analysis of additional AD and control post-mortem human brains showed that the SDIM1 transcript was indeed significantly down regulated in all AD brains. SDIM1 is more abundant in NT2 neurons than astrocytes and present throughout the cytoplasm and neural processes, but not in the nuclei. In NT2 neurons, it is highly responsive to stress conditions mimicking insults that may cause neurodegeneration in AD brains. For example, SDIM1 was significantly down regulated 2 h after oxygen-glucose deprivation (OGD, though had recovered 16 h later, and also appeared significantly up regulated compared to untreated NT2 neurons. Overexpression of SDIM1 in neuro-progenitor cells improved cells' ability to survive after injurious insults and its downregulation accelerated cell death induced by OGD. Yeast two-hybrid screening and co-immunoprecipitation approaches revealed, both in vitro and in vivo, an interaction between SDIM1 and DNAJB4, a heat shock protein hsp40 homolog, recently known as an enhancer of apoptosis that also interacts with the mu opioid receptor in human brain. Overexpression of DNAJB4 alone significantly reduced cell viability and SDIM1 co-overexpression was capable of attenuating the cell death

  20. Multiple Temporalities, Layered Histories

    Directory of Open Access Journals (Sweden)

    Steven Pearson

    2017-11-01

    Full Text Available In Quotational Practices: Repeating the Future in Contemporary Art, Patrick Greaney asserts, “the past matters not only because of what actually happened but also because of the possibilities that were not realized and that still could be. Quotation evokes those possibilities. By repeating the past, artists and writers may be attempting to repeat that past’s unrealized futures.”[1]  In the information age, the Internet, for instance, provides us an expanded collection of visual information—quite literally available at our fingertips—summoning together aspects of the past and possibilities of the future into a boundless present. Sketchbook Revisions (2014–2015, a series of mixed-media paintings, represents my attempt to communicate the ways in which I experience my contemporary moment constructed from multiple temporalities excavated from my past. This body of work combines fragments of representational paintings created between 1995 and 2003 and nonrepresentational renderings produced between 2003 and 2014. Using traditional tracing paper and graphic color, I randomly select moments of my previous work to transfer and layer over selected areas of already-filled pages of a sketchbook I used from 2003 to 2004. These sketches depict objects I encountered in studio art classrooms and iconic architecture on the campus of McDaniel College, and often incorporate teaching notes. The final renditions of fragmented and layered histories enact the ways that we collectively experience multiple temporalities in the present. Quoting my various bodies of work, Sketchbook Revisions challenges both material and conceptual boundaries that determine fixed notions of artistic identity.

  1. Respiratory muscle training for multiple sclerosis

    NARCIS (Netherlands)

    Rietberg, Marc B.; Veerbeek, Janne M.; Gosselink, Rik; Kwakkel, Gert; van Wegen, Erwin E.H.

    2017-01-01

    Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and

  2. A multiplicity jump trigger using silicon planes

    International Nuclear Information System (INIS)

    Alexopoulos, T.; Erwin, A.R.

    1993-01-01

    Since silicon tracking planes are already present in a B decay experiment, it is an attractive idea to use these as part of a multiplicity jump detector. Two average B decays would produce a multiplicity jump of around 10 in the final state. Such a trigger has been tried for a fixed target Charm experiment with disappointing success. The failure was attributed to the difficulty in adequately controlling the gains of a large number of microstrip amplifies

  3. Multiplicities in high energy interactions

    International Nuclear Information System (INIS)

    Derrick, M.

    1984-01-01

    Charged particle multiplicities in hadronic collision have been measured for all energies up to √s = 540 GeV in the center of mass. Similar measurements in e + e - annihilation cover the much smaller range - up to √s = 40 GeV. Data are also available from deep inelastic neutrino scattering up to √s approx. 10 GeV. The experiments measure the mean charged multiplicity , the rapidity density at y = O, and the distributions in prong number. The mean number of photons associated with the events can be used to measure the π 0 and eta 0 multiplicities. Some information is also available on the charged pion, kaon, and nucleon fractions as well as the K 0 and Λ 0 rates and for the higher energy data, the identically equal fraction. We review this data and consider the implications of extrapolations to SSC energies. 13 references

  4. Palliative radiotherapy for multiple myeloma

    International Nuclear Information System (INIS)

    Furusawa, Mitsuhiro; Baba, Yuji; Murakami, Ryuji; Yokoyama, Toshimi; Nishimura, Ryuichi; Uozumi, Hideaki; Takada, Chitose; Takahashi, Mutsumasa

    1995-01-01

    This study reviews the experience of palliative radiotherapy to patients with multiple myeloma to define the optimal dose for pain relief. The records of 31 patients (66 sites) with multiple myeloma irradiated for palliation at Kumamoto University hospital between 1985 and 1994 were reviewed. Total dose ranged from 8 to 50 Gy, with a mean of 32.2 Gy. Symptoms included pain (78.1%), neurological abnormalities (28.1%), and palpable masses (34.3%). Symptomatic remission was obtained in 45 of 46 evaluable sites (97.8%). Complete remission of symptoms were obtained in 28.3%, and partial remission in 69.6%. According to fraction size, there was no significant difference between 3-5 Gy and 1.8-2 Gy. The incidence of complete remission increased when a total dose of more than 20 Gy was given. When the quality of life is considered, hypofractionation was recommended for the palliative radiation therapy of multiple myeloma. (author)

  5. Wide range of interacting partners of pea Gβ subunit of G-proteins suggests its multiple functions in cell signalling.

    Science.gov (United States)

    Bhardwaj, Deepak; Lakhanpaul, Suman; Tuteja, Narendra

    2012-09-01

    Climate change is a major concern especially in view of the increasing global population and food security. Plant scientists need to look for genetic tools whose appropriate usage can contribute to sustainable food availability. G-proteins have been identified as some of the potential genetic tools that could be useful for protecting plants from various stresses. Heterotrimeric G-proteins consisting of three subunits Gα, Gβ and Gγ are important components of a number of signalling pathways. Their structure and functions are already well studied in animals but their potential in plants is now gaining attention for their role in stress tolerance. Earlier we have reported that over expressing pea Gβ conferred heat tolerance in tobacco plants. Here we report the interacting partners (proteins) of Gβ subunit of Pisum sativum and their putative role in stress and development. Out of 90 transformants isolated from the yeast-two-hybrid (Y2H) screening, seven were chosen for further investigation due to their recurrence in multiple experiments. These interacting partners were confirmed using β-galactosidase colony filter lift and ONPG (O-nitrophenyl-β-D-galactopyranoside) assays. These partners include thioredoxin H, histidine-containing phosphotransfer protein 5-like, pathogenesis-related protein, glucan endo-beta-1, 3-glucosidase (acidic isoform), glycine rich RNA binding protein, cold and drought-regulated protein (corA gene) and soluble inorganic pyrophosphatase 1. This study suggests the role of pea Gβ subunit in stress signal transduction and development pathways owing to its capability to interact with a wide range of proteins of multiple functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  6. Over-expression of NAD kinase in Corynebacterium crenatum and ...

    African Journals Online (AJOL)

    in Corynebacterium crenatum SYPA5-5 and to study its impact in presence of high (HOS) ... Results: In HOS condition, NAD+ kinase activity increased by 116 %, while ... (NADPH), an important co-enzyme during ... Polymerase, TaKaRa) using C. crenatum .... were washed with cold 100 mM PBS (pH 7.5) ..... Catalase and.

  7. Contextual control over expression of fear is affected by cortisol

    Directory of Open Access Journals (Sweden)

    Vanessa Anna Van Ast

    2012-10-01

    Full Text Available At the core of anxiety disorders is the inability to use contextual information to modulate behavioral responses to potentially threatening events. Models of the pathogenesis of anxiety disorders incorporate stress and concomitant stress hormones as important vulnerability factors, while others emphasize sex as an important factor. However, translational basic research has not yet investigated the effects of stress hormones and sex on the ability to use contextual information to modulate responses to threat. Therefore, the purpose of the present study was threefold: first, we aimed at developing an experimental paradigm specifically capable of capturing contextual modulation of the expression of fear. Second, we tested whether cortisol would alter the contextualization of fear expression. Third, we aimed at assessing whether alterations in contextualization due to cortisol were different for men and women. Healthy participants (n = 42 received placebo or hydrocortisone (20 mg prior to undergoing a newly developed differential contextual fear conditioning paradigm. The results indicated that people rapidly acquire differential contextual modulation of the expression of fear, as measured by fear potentiated startle and skin conductance responses. In addition, cortisol impaired the contextualization of fear expression leading to increased fear generalization on fear potentiated startle data in women. The opposite pattern was found in men. Finally, as assessed by skin conductance responses, cortisol impaired differential conditioning in men. The results are in line with models suggesting heightened vulnerability in women for developing anxiety disorders after stressful events.

  8. Over-expression of xylanolytic α-glucuronidase from Thermotoga ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-18

    Jul 18, 2008 ... ... at http://www.academicjournals.org/AJB. ISSN 1684–5315 © 2008 Academic Journals .... version 6.0 of the sequence analysis software package (Lynnon. Biosoft, USA). .... the xylan supernatant by nylon fabric. The resulting ...

  9. Over-expression of xylanolytic ∝-glucuronidase from Thermotoga ...

    African Journals Online (AJOL)

    The GH67∝-glucuronidase encoded by aguA of Thermotoga maritima is one of the most ... to date and thus has considerable potential in industrial application. ... Enzymatic hydrolysis of corncob xylan examined by HPLC showed that more ...

  10. New insights into the pathophysiology of multiple myeloma

    International Nuclear Information System (INIS)

    Tothova, E.; Kafkova, A.

    2013-01-01

    The last decade has seen significant advances in our understanding of the biology of multiple myeloma (MM) and our approaches to its treatment. As a result of these advances, the median survival of patients has increased and we can now achieve a cure in at least some patients. This improved knowledge about MM biology needs to be rapidly translated and transformed into diagnostic and therapeutic applications to finally achieve cure in a larger proportion of patients. Genetic mutations leading to chromosomal translocations and deletions play a key role in the progression to active, malignant MM. As a part of these translation efforts, novel drugs that inhibit oncogenic proteins over expressed in defined molecular subgroups of the disease, are currently being developed. Identification of potential therapeutic targets in the bone marrow microenvironment is leading to the development of therapies that are changing the standard of care for MM patients. (author)

  11. Multiple-Ring Digital Communication Network

    Science.gov (United States)

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  12. Search for new phenomena in final states with large jet multiplicities and missing transverse momentum at √s = 8 TeV proton-proton collisions using the ATLAS experiment

    Czech Academy of Sciences Publication Activity Database

    Aad, G.; Abajyan, T.; Abbott, B.; Böhm, Jan; Chudoba, Jiří; Hejbal, Jiří; Jakoubek, Tomáš; Kepka, Oldřich; Kupčo, Alexander; Kůs, Vlastimil; Lokajíček, Miloš; Lysák, Roman; Marčišovský, Michal; Mikeštíková, Marcela; Myška, Miroslav; Němeček, Stanislav; Růžička, Pavel; Schovancová, Jaroslava; Šícho, Petr; Staroba, Pavel; Svatoš, Michal; Taševský, Marek; Tic, Tomáš; Vrba, Václav

    2013-01-01

    Roč. 2013, č. 10 (2013), s. 1-50 ISSN 1029-8479 R&D Projects: GA MŠk(CZ) LG13009 Institutional support: RVO:68378271 Keywords : transverse momentum * missing-energy * scattering * jet * multiplicity * supergravity * minimal * ATLAS * CERN LHC Coll * new particle Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 6.220, year: 2013

  13. Over-Expression of CYP2E1 mRNA and Protein: Implications of Xenobiotic Induced Damage in Patients with De Novo Acute Myeloid Leukemia with inv(16(p13.1q22; CBFβ-MYH11

    Directory of Open Access Journals (Sweden)

    Carlos E. Bueso-Ramos

    2012-08-01

    Full Text Available Environmental exposure to benzene occurs through cigarette smoke, unleaded gasoline and certain types of plastic. Benzene is converted to hematotoxic metabolites by the hepatic phase-I enzyme CYP2E1, and these metabolites are detoxified by the phase-II enzyme NQO1. The genes encoding these enzymes are highly polymorphic and studies of these polymorphisms have shown different pathogenic and prognostic features in various hematological malignancies. The potential role of different cytochrome p450 metabolizing enzymes in the pathogenesis of acute myeloid leukemia (AML in an area of active interest. In this study, we demonstrate aberrant CYP2E1 mRNA over-expression by quantitative real-time polymerase chain reaction in 11 cases of de novo AML with inv(16; CBFβ-MYH11. CYP2E1 mRNA levels correlated with CBFβ-MYH11 transcript levels and with bone marrow blast counts in all cases. CYP2E1 over-expression correlated positively with NQO1 mRNA levels (R2 = 0.934, n = 7. By immunohistochemistry, CYP2E1 protein was more frequently expressed in AML with inv(16 compared with other types of AML (p < 0.001. We obtained serial bone marrow samples from two patients with AML with inv(16 before and after treatment. CYP2E1 mRNA expression levels decreased in parallel with CBFβ-MYH11 transcript levels and blast counts following chemotherapy. In contrast, CYP1A2 transcript levels did not change in either patient. This is the first study to demonstrate concurrent over-expression of CYP2E1 and NQO1 mRNA in AML with inv(16. These findings also suggest that a balance between CYP2E1 and NQO1 may be important in the pathogenesis of AML with inv(16.

  14. Generalized internal multiple imaging

    KAUST Repository

    Zuberi, Mohammad Akbar Hosain

    2014-12-04