bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience-dependent maturation of the glomerular microcircuit
Authors: Maher Brady J. , McGinley Matthew J. , Westbrook Gary L.
Published: September 2009

Spontaneous and patterned activity, largely attributed to chemical transmission, shape the development of virtually all neural circuits. However, electrical transmission also has an important role in coordinated activity in the brain. In the olfactory bulb, gap junctions between apical dendrites of mitral cells increase excitability and synchronize firing within each glomerulus. We report here that the development of the glomerular microcircuit requires both sensory experience and connexin (Cx)36-mediated gap junctions. Coupling coefficients, which measure electrical coupling between mitral cell dendrites, were high in young mice, but decreased after postnatal day (P)10 because of a maturational increase in membrane conductance. Sensory deprivation, induced by unilateral naris occlusion at birth, slowed the morphological development of mitral cells and arrested the maturational changes in membrane conductance and coupling coefficients. As the coupling coefficients decreased in normal mice, a glutamate-mediated excitatory postsynaptic current (EPSC) between mitral cells emerged by P30. Although mitral–mitral EPSCs were generally unidirectional, they were not present in young adult Cx36
−/−
mice, suggesting that gap junctions are required for the development and/or function of the mature circuit. The experience-dependent transition from electrical transmission to combined chemical and electrical transmission provides a previously unappreciated mechanism that may tune the response properties of the glomerular microcircuit.
Survey of large protein complexes in
D. vulgaris
reveals great structural diversity
Authors: Han Bong-Gyoon , Dong Ming , Liu Haichuan , Camp Lauren , Geller Jil , Singer Mary , Hazen Terry C. , Choi Megan , Witkowska H. Ewa , Ball David A. , Typke Dieter , Downing Kenneth H. , Shatsky Maxim , Brenner Steven E. , Chandonia John-Marc , Biggin Mark D. , Glaeser Robert M.
Published: September 2009

An unbiased survey has been made of the stable, most abundant multi-protein complexes in
Desulfovibrio vulgaris
Hildenborough (
Dv
H) that are larger than Mr ≈ 400 k. The quaternary structures for 8 of the 16 complexes purified during this work were determined by single-particle reconstruction of negatively stained specimens, a success rate ≈10 times greater than that of previous “proteomic” screens. In addition, the subunit compositions and stoichiometries of the remaining complexes were determined by biochemical methods. Our data show that the structures of only two of these large complexes, out of the 13 in this set that have recognizable functions, can be modeled with confidence based on the structures of known homologs. These results indicate that there is significantly greater variability in the way that homologous prokaryotic macromolecular complexes are assembled than has generally been appreciated. As a consequence, we suggest that relying solely on previously determined quaternary structures for homologous proteins may not be sufficient to properly understand their role in another cell of interest.
Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine
Authors: Gourley Shannon L. , Koleske Anthony J. , Taylor Jane R.
Published: September 2009

Adolescence is characterized by increased vulnerability to developing neuropsychiatric disorders and involves a period of prefrontal cortical dendritic refinement and synaptic pruning that culminates in cytoskeletal stabilization in adulthood. The Abl-related gene (Arg) acts through p190RhoGAP to inhibit the RhoA GTPase and stabilize cortical dendritic arbors beginning in adolescence. Cortical axons, dendrites, and synapses develop normally in Arg-deficient (
arg
−/−
) mice, but adult dendrites destabilize and regress; thus,
arg
−/−
mice present a model of adolescent-onset dendritic simplification. We show that
arg
−/−
mice are impaired in a reversal task and that deficits are grossly exacerbated by low-dose cocaine administration. Although ventral prefrontal dopamine D2 receptor levels predict “perseverative” error counts in wild-type mice, no such relationship is found in
arg
−/−
mice. Moreover,
arg
−/−
mice are insensitive to the disruptive effects of the D2/D3 antagonist haloperidol in reversal but show normal sensitivity to its locomotor-depressant actions. Arg deficiency and orbitofrontal cortical Arg inhibition via STI-571 infusion also enhance the psychomotor stimulant actions of cocaine. These findings provide evidence that stabilization of dendritic structure beginning in adolescence is critical for the development of adaptive and flexible behavior after cocaine exposure.
No facilitator required for membrane transport of hydrogen sulfide
Authors: Mathai John C. , Missner Andreas , Kügler Philipp , Saparov Sapar M. , Zeidel Mark L. , Lee John K. , Pohl Peter
Published: September 2009

Hydrogen sulfide (H
2
S) has emerged as a new and important member in the group of gaseous signaling molecules. However, the molecular transport mechanism has not yet been identified. Because of structural similarities with H
2
O, it was hypothesized that aquaporins may facilitate H
2
S transport across cell membranes. We tested this hypothesis by reconstituting the archeal aquaporin AfAQP from sulfide reducing bacteria
Archaeoglobus fulgidus
into planar membranes and by monitoring the resulting facilitation of osmotic water flow and H
2
S flux. To measure H
2
O and H
2
S fluxes, respectively, sodium ion dilution and buffer acidification by proton release (H
2
S ⇆ H
+
+ HS
−
) were recorded in the immediate membrane vicinity. Both sodium ion concentration and pH were measured by scanning ion-selective microelectrodes. A lower limit of lipid bilayer permeability to H
2
S,
P

M,H
2
S

≥ 0.5 ± 0.4 cm/s was calculated by numerically solving the complete system of differential reaction diffusion equations and fitting the theoretical pH distribution to experimental pH profiles. Even though reconstitution of AfAQP significantly increased water permeability through planar lipid bilayers,
P

M,H
2
S

remained unchanged. These results indicate that lipid membranes may well act as a barrier to water transport although they do not oppose a significant resistance to H
2
S diffusion. The fact that cholesterol and sphingomyelin reconstitution did not turn these membranes into an H
2
S barrier indicates that H
2
S transport through epithelial barriers, endothelial barriers, and membrane rafts also occurs by simple diffusion and does not require facilitation by membrane channels.
The tyrosine phosphatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development
Authors: Grossmann Katja S. , Wende Hagen , Paul Florian E. , Cheret Cyril , Garratt Alistair N. , Zurborg Sandra , Feinberg Konstantin , Besser Daniel , Schulz Herbert , Peles Elior , Selbach Matthias , Birchmeier Walter , Birchmeier Carmen
Published: September 2009

The nonreceptor tyrosine phosphatase Shp2 (PTPN11) has been implicated in tyrosine kinase, cytokine, and integrin receptor signaling. We show here that conditional mutation of Shp2 in neural crest cells and in myelinating Schwann cells resulted in deficits in glial development that are remarkably similar to those observed in mice mutant for Neuregulin-1 (Nrg1) or the Nrg1 receptors, ErbB2 and ErbB3. In cultured Shp2 mutant Schwann cells, Nrg1-evoked cellular responses like proliferation and migration were virtually abolished, and Nrg1-dependent intracellular signaling was altered. Pharmacological inhibition of Src family kinases mimicked all cellular and biochemical effects of the Shp2 mutation, implicating Src as a primary Shp2 target during Nrg1 signaling. Together, our genetic and biochemical analyses demonstrate that Shp2 is an essential component in the transduction of Nrg1/ErbB signals.
Subcellular localization of a bacterial regulatory RNA
Authors: Russell Jay H. , Keiler Kenneth C.
Published: September 2009

Eukaryotes and bacteria regulate the activity of some proteins by localizing them to discrete subcellular structures, and eukaryotes localize some RNAs for the same purpose. To explore whether bacteria also spatially regulate RNAs, the localization of tmRNA was determined using fluorescence
in situ
hybridization. tmRNA is a small regulatory RNA that is ubiquitous in bacteria and that interacts with translating ribosomes in a reaction known as
trans
-translation. In
Caulobacter crescentus
, tmRNA was localized in a cell-cycle–dependent manner. In G
1
-phase cells, tmRNA was found in regularly spaced foci indicative of a helix-like structure. After initiation of DNA replication, most of the tmRNA was degraded, and the remaining molecules were spread throughout the cytoplasm. Immunofluorescence assays showed that SmpB, a protein that binds tightly to tmRNA, was colocalized with tmRNA in the helix-like pattern. RNase R, the nuclease that degrades tmRNA, was localized in a helix-like pattern that was separate from the SmpB-tmRNA complex. These results suggest a model in which tmRNA-SmpB is localized to sequester tmRNA from RNase R, and localization might also regulate tmRNA-SmpB interactions with ribosomes.
Mediator complex association with constitutively transcribed genes in yeast
Authors: Ansari Suraiya A. , He Qiye , Morse Randall H.
Published: September 2009

Mediator is a large, multisubunit complex that is essential for transcription of mRNA by RNA Pol II in eukaryotes and is believed to bridge transcriptional activators and the general transcription machinery. However, several recent studies suggest that the requirement for Mediator during transcriptional activation is not universal, but rather activator dependent, and may be indirect for some genes. Here we have investigated Mediator association with several constitutively transcribed genes in yeast by comparing a yeast strain that harbors a temperature-sensitive mutation in an essential Mediator subunit, Srb4, with its wild-type (WT) counterpart. We find modest association of Mediator with constitutively active genes and show that this association is strongly decreased in
srb4 ts
yeast, whereas association with a nontranscribed region or repressed gene promoters is lower and unaffected in the mutant yeast. The tail module of Mediator remains associated with ribosomal protein (RP) gene promoters in
srb4 ts
yeast, while subunits from the head and middle modules are lost. Tail module association at Rap1-dependent gene promoters is lost in
rap1 ts
yeast, indicating that Rap1 is required for Mediator recruitment at these gene promoters and that its recruitment occurs via the tail module. Pol II association is also rapidly and severely affected in
srb4 ts
yeast, indicating that Mediator is directly required for pol II association at constitutively transcribed genes. Our results are consistent with Mediator functioning as a general transcription factor in yeast.
Short-distance probes for protein backbone structure based on energy transfer between bimane and transition metal ions
Authors: Taraska Justin W. , Puljung Michael C. , Zagotta William N.
Published: September 2009

The structure and dynamics of proteins underlies the workings of virtually every biological process. Existing biophysical methods are inadequate to measure protein structure at atomic resolution, on a rapid time scale, with limited amounts of protein, and in the context of a cell or membrane. FRET can measure distances between two probes, but depends on the orientation of the probes and typically works only over long distances comparable with the size of many proteins. Also, common probes used for FRET can be large and have long, flexible attachment linkers that position dyes far from the protein backbone. Here, we improve and extend a fluorescence method called transition metal ion FRET that uses energy transfer to transition metal ions as a reporter of short-range distances in proteins with little orientation dependence. This method uses a very small cysteine-reactive dye monobromobimane, with virtually no linker, and various transition metal ions bound close to the peptide backbone as the acceptor. We show that, unlike larger fluorophores and longer linkers, this donor–acceptor pair accurately reports short-range distances and changes in backbone distances. We further extend the method by using cysteine-reactive metal chelators, which allow the technique to be used in protein regions of unknown secondary structure or when native metal ion binding sites are present. This improved method overcomes several of the key limitations of classical FRET for intramolecular distance measurements.
BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken
Authors: Goto Ronald M. , Wang Yujun , Taylor Robert L. , Wakenell Patricia S. , Hosomichi Kazuyoshi , Shiina Takashi , Blackmore Craig S. , Briles W. Elwood , Miller Marcia M.
Published: September 2009

Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-
B
haplotype and the occurrence of virally induced tumors in the chicken provides a means for defining the relationship between pathogen selection and MHC polymorphism. Here, we verified a significant difference in resistance to gallid herpesvirus-2 (GaHV-2)-induced lymphomas (Marek's disease) conferred by two closely-related recombinant MHC-
B
haplotypes. We mapped the crossover breakpoints that distinguish these haplotypes to the highly polymorphic
BG1
locus.
BG1
encodes an Ig-superfamily type I transmembrane receptor-like protein that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized by Src homology
2
domain-containing protein tyrosine phosphatase (SHP-2). The recombinant haplotypes are identical, except for differences within the
BG1
3′-untranslated region (3′-UTR). The 3′-UTR of the
BG1
allele associated with increased lymphoma contains a 225-bp insert of retroviral origin and showed greater inhibition of luciferase reporter gene translation compared to the other allele. These findings suggest that
BG1
could affect the outcome of GaHV-2 infection through modulation of the lymphoid cell responsiveness to infection, a condition that is critical for GaHV-2 replication and in which the MHC-
B
haplotype has been previously implicated. This work provides a mechanism by which MHC-
B
region genetics contributes to the incidence of GaHV-2-induced malignant lymphoma in the chicken and invites consideration of the possibility that similar mechanisms might affect the incidence of lymphomas associated with other oncogenic viral infections.
Strong-field control and spectroscopy of attosecond electron-hole dynamics in molecules
Authors: Smirnova Olga , Patchkovskii Serguei , Mairesse Yann , Dudovich Nirit , Ivanov Misha Yu
Published: September 2009

Molecular structures, dynamics and chemical properties are determined by shared electrons in valence shells. We show how one can selectively remove a valence electron from either Π vs. Σ or bonding vs. nonbonding orbital by applying an intense infrared laser field to an ensemble of aligned molecules. In molecules, such ionization often induces multielectron dynamics on the attosecond time scale. Ionizing laser field also allows one to record and reconstruct these dynamics with attosecond temporal and sub-Ångstrom spatial resolution. Reconstruction relies on monitoring and controlling high-frequency emission produced when the liberated electron recombines with the valence shell hole created by ionization.
Spatiotemporal patterns and transcription kinetics of induced RNA in single bacterial cells
Authors: Valencia-Burton Maria , Shah Ankita , Sutin Jason , Borogovac Azra , McCullough Ron M. , Cantor Charles R. , Meller Amit , Broude Natalia E.
Published: September 2009

Bacteria have a complex internal organization with specific localization of many proteins and DNA, which dynamically move during the cell cycle and in response to changing environmental stimuli. Much less is known, however, about the localization and movements of RNA molecules. By modifying our previous RNA labeling system, we monitor the expression and localization of a model RNA transcript in live
Escherichia coli
cells. Our results reveal that the target RNA is not evenly distributed within the cell and localizes laterally along the long cell axis, in a pattern suggesting the existence of ordered helical RNA structures reminiscent of known bacterial cytoskeletal cellular elements.
Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress
Authors: Hains Avis Brennan , Vu Mai Anh T. , Maciejewski Paul K. , van Dyck Christopher H. , Gottron Melissa , Arnsten Amy F. T.
Published: September 2009

The prefrontal cortex r regulates behavior, cognition, and emotion by using working memory. Prefrontal functions are impaired by stress exposure. Acute, stress-induced deficits arise from excessive protein kinase C (PKC) signaling, which diminishes prefrontal neuronal firing. Chronic stress additionally produces architectural changes, reducing dendritic complexity and spine density of cortico-cortical pyramidal neurons, thereby disrupting excitatory working memory networks. In vitro studies have found that sustained PKC activity leads to spine loss from hippocampal-cultured neurons, suggesting that PKC may contribute to spine loss during chronic stress exposure. The present study tested whether inhibition of PKC with chelerythrine before daily stress would protect prefrontal spines and working memory. We found that inhibition of PKC rescued working memory impairments and reversed distal apical dendritic spine loss in layer II/III pyramidal neurons of rat prelimbic cortex. Greater spine density predicted better cognitive performance, the first direct correlation between pyramidal cell structure and working memory abilities. These findings suggest that PKC inhibitors may be neuroprotective in disorders with dysregulated PKC signaling such as bipolar disorder, schizophrenia, post-traumatic stress disorder, and lead poisoning—conditions characterized by impoverished prefrontal structural and functional integrity.
Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans
Authors: Xu Bin , Woodroffe Abigail , Rodriguez-Murillo Laura , Roos J. Louw , van Rensburg Elizabeth J. , Abecasis Gonçalo R. , Gogos Joseph A. , Karayiorgou Maria
Published: September 2009

To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease.
Structure of a tRNA-dependent kinase essential for selenocysteine decoding
Authors: Araiso Yuhei , Sherrer R. Lynn , Ishitani Ryuichiro , Ho Joanne M. L. , Söll Dieter , Nureki Osamu
Published: September 2009

Compared to bacteria, archaea and eukaryotes employ an additional enzyme for the biosynthesis of selenocysteine (Sec), the 21
st
natural amino acid (aa). An essential RNA-dependent kinase,
O
-phosphoseryl-tRNA
Sec
kinase (PSTK), converts seryl-tRNA
Sec
to
O
-phosphoseryl-tRNA
Sec
, the immediate precursor of selenocysteinyl-tRNA
Sec
. The sequence of
Methanocaldococcus jannaschii
PSTK (MjPSTK) suggests an N-terminal kinase domain (177 aa) followed by a presumed tRNA binding region (75 aa). The structures of MjPSTK complexed with ADP and AMPPNP revealed that this enzyme belongs to the P-loop kinase class, and that the kinase domain is closely related to gluconate kinase and adenylate kinase. ATP is bound by the P-loop domain (residues 11–18). Formed by antiparallel dimerization of two PSTK monomers, the enzyme structure shows a deep groove with positive electrostatic potential. Located in this groove is the enzyme's active site, which biochemical and genetic data suggest is composed of Asp-41, Arg-44, Glu-55, Tyr-82, Tyr-83, Met-86, and Met-132. Based on structural comparison with
Escherichia coli
adenylate kinase a docking model was generated that assigns these amino acids to the recognition of the terminal A76-Ser moieties of Ser-tRNA
Sec
. The geometry and electrostatic environment of the groove in MjPSTK are perfectly complementary to the unusually long acceptor helix of tRNA
Sec
.
Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA
Authors: Wang Gang , Cui Ying , Zhang Guangfeng , Garen Alan , Song Xu
Published: September 2009

We describe the role of PSF protein and VL30–1 RNA, a mouse retroelement noncoding RNA, in the reversible regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice. The experiments involved increasing expression of PSF or VL30–1 RNA in NIH/3T3 fibroblast cells and B16F10 melanoma cells by transfecting the respective coding genes under control of a strong promoter or decreasing expression by transfecting a shRNA construct that causes degradation of PSF mRNA or VL30–1 RNA. The results are as follows: (
i
) PSF binds to the proto-oncogene
Rab23
, repressing transcription, and VL30–1 RNA binds and releases PSF from
Rab23
, activating transcription; (
ii
) increasing expression of PSF or decreasing expression of VL30–1 RNA suppresses cell proliferation in culture and tumorigenesis in mice; and (
iii
) decreasing expression of PSF or increasing expression of VL30–1 RNA promotes cell proliferation in culture and tumorigenesis in mice. These results indicate that PSF is a major tumor-suppressor protein and VL30–1 RNA is a major tumor-promoter RNA in mice. Although VL30–1 RNA can integrate into the cell genome, tumor promotion by VL30–1 RNA involves a
trans
effect rather than a
cis
effect on gene transcription. Expression of VL30–1 RNA is 5- to 8-fold higher in mouse tumor lines than in mouse fibroblast or myoblast lines, whereas expression of PSF mRNA does not decrease in the tumor lines, suggesting that tumorigenesis is driven by an increase of VL30–1 RNA rather than a decrease of PSF. A similar regulatory mechanism functions in human cells, except that human PSF-binding RNAs replace VL30–1 RNA, which is not encoded in the human genome. We propose that PSF protein and PSF-binding RNAs have a central role in the reversible regulation of mammalian cell proliferation and tumorigenesis and that increasing PSF expression or decreasing PSF-binding RNA expression in tumor cells is a potential therapeutic strategy for cancer.
Direct observation of barrier-limited folding of BBL by single-molecule fluorescence resonance energy transfer
Authors: Huang Fang , Ying Liming , Fersht Alan R.
Published: September 2009

One controversial area in protein folding mechanisms is whether some small, ultra-fast-folding proteins exist in distinct native and denatured state ensembles, separated by an energy barrier, or if there is a continuum of states between native and denatured. In theory, the simplest way of distinguishing between single-state barrierless or “downhill” folding and conventional separate state folding is by single-molecule spectroscopy, which can detect either distinct populations of proteins or a continuum. But, the time resolution of approximately 1 ms of most confocal fluorescence microscopes for single-molecule fluorescence resonance energy transfer (SM-FRET) is longer than that for the structural relaxation of proteins such as BBL, whose mechanism of folding is controversial. We have constructed a highly sensitive confocal fluorescence microscope and measured the distribution of FRET efficiencies of appropriately labeled BBL in time bins of 50 and 200 μs under conditions in which its structural relaxation time is 340 μs or less. The experiments are at the very limits of detection because of signal artefacts from shot noise, photo-bleaching, and other events that broaden signals of individual states so they appear to coalesce. However, with appropriate tuning of the thresholds for detection and length of data collection, we clearly observed 2 distinct states of BBL, with FRET efficiencies corresponding to native and denatured states. The population of each state varied with GdmCl or urea during chemical denaturation transitions corresponding to conventional barrier-limited folding at 279 K and pH 7 and pH 5.8. The folding of BBL is accordingly barrier limited.
Gas Plasma Sterilization -- Application of Space-Age Technology
Authors: Crow Sue , Smith John H.
Published: September 2009

Gas plasma sterilization is new to the healthcare field. The first such sterilizer has been manufactured by Advanced Sterilization Products (J&J, Irvine, CA). The system uses hydrogen peroxide as the substrate gas and radio frequency emissions to generate plasma. This system is a low-temperature, quick-acting process with no toxic residues. It appears that this sterilizer system holds promise in the healthcare field and could help to reduce the use of ethylene oxide.
Plasma physics and laser development for the Fast-Ignition Realization Experiment (FIREX) Project
Authors: Azechi H. , Mima K. , Fujimoto Y. , Fujioka S. , Homma H. , Isobe M. , Iwamoto A. , Jitsuno T. , Johzaki T. , Kodama R. , Koga M. , Kondo K. , Kawanaka J. , Mito T. , Miyanaga N. , Motojima O. , Murakami M. , Nagatomo H. , Nagai K. , Nakai M. , Nakamura H. , Nakamura T. , Nakazato T. , Nakao Y. , Nishihara K. , Nishimura H. , Norimatsu T. , Ozaki T. , Sakagami H. , Sakawa Y. , Sarukura N. , Shigemori K. , Shimizu T. , Shiraga H. , Sunahara A. , Taguchi T. , Tanaka K.A. , Tsubakimoto K.
Published: September 2009

Since the approval of the first phase of the Fast-Ignition Realization Experiment (FIREX-I), we have devoted our efforts to designing advanced targets and constructing a petawatt laser, which will be the most energetic petawatt laser in the world. Scientific and technological improvements are required to efficiently heat the core plasma. There are two methods that can be used to enhance the coupling efficiency of the heating laser to the thermal energy of the compressed core plasma: adding a low-Z foam layer to the inner surface of the cone and employing a double cone. The implosion performance can be improved in three ways: adding a low-Z plastic layer to the outer surface of the cone, using a Br-doped plastic ablator and evacuating the target centre. An advanced target for FIREX-I was introduced to suit these requirements. A new heating laser (LFEX) has been constructed that is capable of delivering an energy of 10 kJ in 10 ps with a 1 ps rise time. A fully integrated fast-ignition experiment is scheduled for 2009.
Effect of cross-field drifts on flows in the main scrape-off-layer of DIII-D L-mode plasmas
Authors: Groth M. , Boedo J.A. , Brooks N.H. , Isler R.C. , Leonard A.W. , Porter G.D. , Watkins J.G. , West W.P. , Bray B.D. , Fenstermacher M.E. , Groebner R.J. , Moyer R.A. , Rudakov D.L. , Yu J.H. , Zeng L.
Published: September 2009

The flow velocities of deuterons and low charge-state carbon ions have been measured simultaneously in the main scrape-off-layer (SOL) in low-density plasmas in DIII-D, and the dependences of these flow fields on the direction of the cross-field drifts (
E
×
B
and
B
× ∇B) have been investigated. These measurements were taken poloidally localized in the SOL region vertically opposite the divertor X-point. The carbon ion flows do not necessarily match those of the deuterons either in the direction with respect to the magnetic field lines or in magnitude, suggesting that physics effects apart from entrainment play a significant role in the impurity response. In configurations with the ion
B
× ∇B drift towards the divertor X-point, the parallel-
B
deuteron velocities at the plasma crown are high (−20 to −30 km s−1 in the direction of the high field side (HFS) divertor), while they are nearly zero in configurations with the opposite
B
× ∇B drift direction. The flow direction of singly and doubly charged carbon ions is independent of the ion
B
× ∇B drift direction, and the ions flow at approximately −5 to −10 km s−1 towards the HFS divertor. Simulations with the UEDGE code have been carried out to better understand the underlying physics processes. Inclusion of cross-field drifts in the simulations produced divertor solutions for density and temperature that agree significantly better with measured divertor parameters. These simulations do not, however, reproduce the measured flow fields at the crown for the configuration with the ion
B
× ∇B drift towards the divertor X-point. The UEDGE code has also been used to understand the influence of pumping at the HFS divertor plate, and a poloidal dependence in the radial transport coefficient.
Electron Bernstein wave heating via the slow X–B mode conversion process with direct launching from the high field side in LHD
Authors: Igami H. , Yoshimura Y. , Kubo S. , Shimozuma T. , Takahashi H. , Tanaka H. , Nagasaki K. , Inagaki S. , Mutoh T. , Komori A.
Published: September 2009

In the Large Helical Device (LHD), direct oblique launching of the fundamental extraordinary (X-) mode from the high magnetic field side (HFS) is available without installation of any additional launching equipment on the inner side wall of the torus. In the experiment, power absorption was observed in two separated regions by the X-mode launching. The central electron density was about 8% of the cutoff density. The result of numerical analysis with the ray-tracing calculation suggests that most power of the launched X-mode is damped out as the X-mode in the fundamental electron cyclotron resonance (ECR) layer before it reaches the upper hybrid resonance (UHR) layer where the electron Bernstein wave (EBW) occurs which is excited via the slow X (SX-) B mode conversion process. Only about 0.2% of the launched power is mode converted to the EBW and is then absorbed at a maximum. One of the two separated power absorption regions observed in the experiment agrees well with the power absorption region of the X-mode suggested by the ray tracing. The other one agrees well with that of the O-mode despite the setting of the X-mode launching. Supposedly mixed waves of the X- and the O-mode might be launched in the experiment. We assumed that the incident transverse electromagnetic waves in vacuum couple with the electromagnetic modes in the plasma at the last closed flux surface (LCFS). However, the coupling point was supposedly located outside the LCFS.

For the few rays that can reach the UHR layer we have recognized that the parallel component of the refractive index N
∥ becomes close to zero and power absorption as the X-mode weakens when the rays pass through the fundamental ECR layer. A numerical investigation assuming a higher central electron density, that is 23% of the cutoff density, suggests a scenario of effective EBW excitation. The ray that passes through the centre of the focused Gaussian beam launched from the HFS so that N
∥ becomes close to zero near the ECR layer, Z can reach the UHR layer without being damped out and excite EBW. About 71% of power of the launched X-mode is mode converted to the EBW and absorbed in the Doppler-shifted ECR layer.

Observation of the parametric decay waves suggests that the decay wave was excited in the ‘exterior’ UHR layer which is located outside the LCFS before the launched X-mode reaches the HFS. The combination of tunnelling, reflection and mode-coupling processes, the so-called ‘Budden's problem’, is suggested to occur in the evanescent region between the ‘exterior’ right handed cyclotron cutoff and the UHR layer outside the LCFS. The tunnelling rate should be considered for estimating the power that can penetrate inside the LCFS from the HFS, in particular in the higher density regime where the excitation of the EBW is expected.
Irradiation effects on reduced activation ferritic/martensitic steels—tensile, impact, fatigue properties and modelling
Authors: Jitsukawa Shiro , Suzuki Kazuhiko , Okubo Nariaki , Ando Masami , Shiba Kiyoyuki
Published: September 2009

At temperatures below 400 °C, irradiation often causes hardening and reduction of elongation as well as toughness degradation to a considerable degree. Data, however, indicate that these changes remain in manageable ranges for ITER-TBM application. Moreover, the saturation tendency of these changes with neutron dose suggests that some of the reduced activation ferritic/martensitic steels are feasible even for future DEMO applications. It is also stressed that the development of a design methodology that is compatible with the large irradiation induced property changes is essential to enable these applications. Modelling activities for the macroscopic mechanical response are expected to play key roles in design methodology development. Macroscopic models of plasticity (a constitutive equation) and cyclic softening behaviour after irradiation are discussed. The significance of the models for estimating microstructural change during irradiation and beneficial effects of the heat treatment for irradiation performance are also introduced.
Bifurcation behaviour of rotation velocities in collisional edge plasma with steep gradients
Authors: Daybelge U. , Yarim C. , Nicolai A.
Published: September 2009

Rotations in both poloidal and toroidal directions of a tokamak edge plasma have important interactions with various other plasma phenomena including plasma stability and transport. Solutions for rotation velocities were studied, using differential equations comprising the ambipolarity constraint and the parallel momentum balance equations of the revisited neoclassical theory, with the corrected contribution also from the gyro-viscosity tensor. Temperature and density profiles with realistic pedestal forms were considered given and controlled parametrically. The similarity of this equation system to reaction–diffusion equations was utilized in the numerical simulation and the study of critical points on the bifurcation diagrams. It was found that the steepness of the density and temperature gradients has important effects on the rotation stability and on its bifurcative behaviour.
Fast dynamics of type I and grassy ELMs in JT-60U
Authors: Kojima A. , Oyama N. , Sakamoto Y. , Kamada Y. , Urano H. , Kamiya K. , Fujita T. , Kubo H. , Aiba N.
Published: September 2009

In order to understand the physics of the ELM trigger and determine the ELM size, the fast ELM dynamics of type I and grassy ELMs have been studied in JT-60U, using new fast diagnostics with high spatial and temporal resolutions such as a lithium beam probe (Δt ∼ 0.5 ms) and a charge exchange recombination spectroscopy (Δt ∼ 2.5 ms), which can measure the electron density and the ion temperature, respectively. The evolution of the ion pressure profile in the pedestal region has been evaluated for the first time by detailed edge profile measurements. Then, the dynamics of the density, the ion temperature and the ion pressure in the ELM cycle has been investigated. The co-rotating plasmas are compared with the counter (ctr)-rotating plasmas for the understanding of the toroidal rotation effects. Type I ELMs observed in co-rotating plasmas exhibit a larger and wider ELM affected area (Δn
ped/n
ped ∼ 30%, radial extent >15 cm) than ctr-rotating plasmas (Δn
ped/n
ped ∼ 20%, radial extent ∼10 cm). Just before a type I ELM crash, the pedestal ion pressure and its maximum gradient in co-rotating plasmas are 20% and 12% higher than those in ctr-rotating plasmas, respectively. It is found that the radial extent of the ion pressure gradient at the pedestal region in co-rotating plasmas is 14% wider than that in ctr-rotating plasmas. The experimental results suggest that the ELM size is connected with the structure of the plasma pressure in the whole pedestal region. As for the dynamics of grassy ELMs, the collapse of density pedestal is smaller (<20%) and narrower (∼5 cm) than those of type I ELMs, as observed in the collapse of the electron temperature pedestal. Thus, it is confirmed that both conductive and convective losses due to grassy ELMs are small.
Investigations of impurity seeding and radiation control for long-pulse and high-density H-mode plasmas in JT-60U
Authors: Asakura N. , Nakano T. , Oyama N. , Sakamoto T. , Matsunaga G. , Itami K.
Published: September 2009

Rseduction of heat loading appropriate for the plasma facing components such as the divertor is crucial for a fusion reactor. Power handling by large radiative power loss has been studied in long pulse ELMy H-mode discharges on JT-60U (τd = 30–35 s). Case 1 is argon (Ar) seeding into standard ELMy H-mode plasmas, where large radiation loss in the confined region of the main plasma caused a change in ELM characteristics from Type-I to Type-III. Case 2 is a combination of Ar and nitrogen (Ne) gas seeding into Type-I ELMy H-mode plasmas with an internal transport barrier (ITB). For case 1, large radiation loss both from the main plasma and from the divertor was produced, and operation of Type-III ELMs was preferable to a reduction in ELM energy loss fraction (W
ELM/W
dia) to 0.15%. Both transient and steady-state heat loadings were reduced. Relatively good energy confinement (H
H98y2 = 0.87 − 0.75) with large f
rad (P
rad/P
abs > 0.8) and divertor plasma detachment was sustained continuously for 13.5 s. For case 2, with reduced Ar seeding to the main plasma and increased divertor radiation with Ne seeding, the ELMy H-mode plasma with an ITB had better energy confinement (H
H98y2 = 0.95 − 0.8), which was sustained continuously for 12 s. The radiated power was increased primarily in the divertor (
), which was produced both by seeded Ne ions and by carbon influx due to transient (ELM) and steady-state heat loadings in the attached divertor. Reduction in the heat loading was not enough, thus enhancement of the radiated power in the divertor will be necessary for the formation of the divertor detachment.
Design windows and cost analysis on a helical reactor
Authors: Kozaki Y. , Imagawa S. , Sagara A.
Published: September 2009

Based on the recent experimental results of the LHD and the magnet technology–cost basis developed for the ITER construction, the design windows of helical reactors are analysed. For searching design windows and investigating their economical potential, we have developed a mass–cost estimating model linked with the system design code (HeliCos). We found that the LHD-type helical reactor has the technically and economically attractive design windows, where the major radius is increased as large as for the sufficient blanket space, but the magnetic stored energy is decreased to a reasonable level because of lower magnetic field with the convenient physics basis of the H factor near 1.1 to the ISS04 scaling and beta value of 5%.
ETG turbulence effects on the evolution of an NTM
Authors: Sen A. , Singh R. , Chandra D. , Kaw P. , Raju D.
Published: September 2009

We study the effect of a background of microturbulence generated by unstable short scale length electron temperature gradient (ETG) modes on the excitation and nonlinear evolution of neoclassical tearing modes (NTMs) in a tokamak. A self-consistent model calculation is carried out in which low frequency stresses generated by the ETG modes act on the NTM and which in turn acts back on the ETG evolution by modulating the turbulence profile. The principal physical consequences of the ETG turbulence are to create an anomalous current diffusivity and an anomalous resistivity contribution. These turbulent transport contributions are incorporated in the evolution equations of a single helicity NTM to obtain a generalized Rutherford equation, and their impact on the instability threshold and growth rate is discussed.
Thermo-mechanical and neutron lifetime modelling and design of Be pebbles in the neutron multiplier for the LIFE engine
Authors: DeMange P. , Marian J. , Caro M. , Caro A.
Published: September 2009

Concept designs for the laser inertial fusion/fission energy (LIFE) engine include a neutron multiplication blanket containing Be pebbles flowing in a molten salt coolant. These pebbles must be designed to withstand the extreme irradiation and temperature conditions in the blanket to enable a reliable and cost-effective operation of LIFE. In this work, we develop design criteria for spherical Be pebbles on the basis of their thermo-mechanical behaviour under continued neutron exposure. We consider the effects of high fluence and fast fluxes on the elastic, thermal and mechanical properties of nuclear-grade Be. Our results suggest a maximum pebble diameter of 30 mm to avoid tensile failure, coated with an anti-corrosive, high-strength metallic shell to avoid failure by pebble contact. Moreover, we find that the operation temperature must always be kept above 450 °C to enable creep to relax the stresses induced by swelling. Under these circumstances, we estimate the pebble lifetime to be at least 16 months if uncoated, and up to six years when coated. We identify the sources of uncertainty on the properties used and discuss the advantages of new intermetallic beryllides and their use in LIFE's neutron multiplier. To establish Be-pebble lifetimes with improved confidence, reliable experiments to measure irradiation creep must be performed.
Menopause and gynaecological disorders: a life course perspective
Authors: Crawford Sybil , Johannes Catherine
Published: September 2009

This chapter reviews the factors at each stage of life that affect timing of the menopause, common urogenital disorders and the decision to have a hysterectomy, and the level of symptomatology experienced during the menopause transition and the decision to take hormone replacement therapy (HRT). In particular, it considers whether developmental processes or early life experiences influence these outcomes in addition to genetic and adult social and biological factors.
Introduction
Authors: Meinert Curtis L. , Tonascia Susan
Published: September 2009

This introduction chapter begins with a brief discussion of the definition of a clinical trial. It then presents a historical sketch of clinical trials followed by a terminology of conventions. The chapter then defines the class of trials considered in this book.
Impact of clinical trials on the practice of medicine
Authors: Meinert Curtis L. , Tonascia Susan
Published: September 2009

This chapter discusses factors that influence the way in which results from trials are viewed and used in everyday medical practice. The University Group Diabetes Program is used as case study.
Quality assurance
Authors: Meinert Curtis L. , Tonascia Susan
Published: September 2009

Quality assurance, as applied to clinical trials, is any method or procedure for collecting, processing, or analyzing study data that is aimed at maintaining or enhancing their reliability or validity. This chapter details the general procedures needed to ensure the quality of the data generated in a trial. Topics covered include ongoing data intake, data editing, replication as a quality control measure, monitoring for secular trends, and data integrity and assurance procedures.
Health Equity: Perspectives, Measurability, and Criteria
Authors: SEN AMARTYA
Published: September 2009

This chapter continues the measurement discussion with a consideration of some of the greatest challenges inherent in attempts to measure inequities in health. It raises the question of what the informational basis should be for assessing health. Ideas of good health and ill health are themselves open to debate. What kind of information should we use to judge the relative goodness or badness of health? A critical distinction concerns the difference between the “internal” and “external” views of illness and health. Should we go by self-perception of bad health (what the patient herself thinks), or should we concentrate, instead, on professional assessment of illness and indifferent health? This also raises a question about the relevance and usefulness of indirect indicators (such as mortality rates and life expectancy).
United States: Social Inequality and the Burden of Poor Health
Authors: KUBZANSKY LAURA D. , KRIEGER NANCY , KAWACHI ICHIRO , ROCKHILL BEVERLY , STEEL GILLIAN K. , BERKMAN LISA F.
Published: September 2009

The United States has the dubious distinction of ranking first among industrialized nations in inequalities in both income and wealth. It also manifests poorer health than many other developed nations and has experienced growing socioeconomic inequalities in health. This chapter draws attention to ways that inequality both shortens and impairs people's lives by focusing on premature mortality and functional disability. It measures health inequity as the disparity in these health outcomes across race/ethnicity, gender, and income group, as experienced in representative samples of the U.S. population. The results give a sense of both the relative unfairness and the burden of poor health in the United States. The chapter argues for the assessment of the full impact of disparities in health across the social gradient, not just on those at highest risk.
Russia: Socioeconomic Dimensions of the Gender Gap in Mortality
Authors: SHKOLNIKOV VLADIMIR M. , FIELD MARK G. , ANDREEV EVGUENIY M.
Published: September 2009

Russia experienced a steep mortality increase after the collapse of the Soviet Union in 1991 and the liberalization of prices in 1992. The existing evidence suggests that the health crisis of the early 1990s can be related to certain socioeconomic and socio-psychological factors such as labor market shocks and stresses, growing income inequalities and relative deprivation, lack of law and order, and decline of social cohesion. One striking development, however, was that the mortality trends in Russia were comparatively worse for men than for women. By the mid-1990s, the gender gap in life expectancy at birth exceeded thirteen years and was at a level approximately double that of other industrialized countries, and four years greater than it was in Russia in the 1960s. This chapter provides an analysis of the socioeconomic dimensions of this gender gap to reveal underlying causes and consequences.