bluuebunny/crossref_metadata_2025 huggingface dataset:
In-cluster-structured exchange-coupled magnets with high energy densities
Authors: Rui X. , Shield J. E. , Sun Z. , Xu Y. , Sellmyer D. J.
Published: September 2006

In this letter, the authors demonstrate isotropic Fe–Pt exchange-spring nanocomposite permanent magnets with a soft magnetic phase fraction of greater than 0.5 with a coercivity of 6.5kOe, single-phase-like magnetic behavior, and an energy product of 25.1MGOe. Sub-10-nm Fe–Pt clusters are formed with compositions in the two-phase Fe3Pt and FePt regions. Intracluster structuring on a scale of a few nanometers occurs after appropriate heat treatment. This ensures full exchange coupling between the two phases, allowing greater soft magnetic phase fractions. The results provide insight into developing high energy product nanostructured permanent magnets.
Band gap and band offsets for ultrathin (HfO2)x(SiO2)1−x dielectric films on Si (100)
Authors: Jin H. , Oh S. K. , Kang H. J. , Cho M.-H.
Published: September 2006

Energy band profile of ultrathin Hf silicate dielectrics, grown by atomic layer deposition, was studied by using x-ray photoelectron spectroscopy and reflection electron energy loss spectroscopy. The band gap energy only slightly increases from 5.52eV for (HfO2)0.75(SiO2)0.25 to 6.10eV for (HfO2)0.25(SiO2)0.75, which is much smaller than 8.90eV for SiO2. For ultrathin Hf silicate dielectrics, the band gap is mainly determined by the Hf 5d conduction band state and the O 2p valence band state. The corresponding conduction band offsets are in the vicinity of 1eV, which satisfies the minimum requirement for the carrier barrier heights.
Highly efficient liquid crystal based diffraction grating induced by polarization holograms at the aligning surfaces
Authors: Provenzano C. , Pagliusi P. , Cipparrone G.
Published: September 2006

Low-scattering and highly efficient orientational gratings are obtained, exploiting polarization holography to modulate the in-plane anchoring axis at both surfaces of a planar nematic cell. Polarization-sensitive azo-dye-doped polyimide films are used as aligning layers. For proper values of cell thickness and spatial periodicity of the gratings, the director configuration in the nematic bulk is a perfect replica of the polarization gratings recorded on the aligning layers. High first-order diffraction efficiency, up to 98%, is observed in thin grating regime. External ac voltage allows to adjust the efficiency over the whole range for arbitrary cell thickness.
Enhancement of in-field Jc in MgB2∕Fe wire using single- and multiwalled carbon nanotubes
Authors: Kim J. H. , Yeoh W. K. , Qin M. J. , Xu X. , Dou S. X. , Munroe P. , Kumakura H. , Nakane T. , Jiang C. H.
Published: September 2006

The authors investigated the doping effects of single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) on the Tc, lattice parameters, Jc(B), microstructure, and Hc2 of MgB2∕Fe wire. These effects systematically showed the following sequence for Tc and the a axis: the SWCNT doped wire<the MWshortCNT doped wire<the MWlongCNT doped wirethe MWshortCNT doped wire>the MWlongCNT doped wire>undoped wire. A dominating mechanism behind all these findings is the level of C substitution for B in the lattice.
Polarization-discriminated spectra of a fiber-microsphere system
Authors: Konishi Hidenori , Fujiwara Hideki , Takeuchi Shigeki , Sasaki Keiji
Published: September 2006

Polarization-discriminated spectra of a fiber-microsphere system were acquired. The authors have succeeded in developing a single-mode tapered fiber capable of maintaining the polarization of the probe beam. The spectra acquired from this system discriminated between transverse electric and transverse magnetic modes.
Thermal behavior of random lasing in dye doped nematic liquid crystals
Authors: Ferjani S. , Barna V. , De Luca A. , Versace C. , Scaramuzza N. , Bartolino R. , Strangi G.
Published: September 2006

The role of the thermally modulated order parameter in the diffusive laser action observed in dye doped nematic liquid crystals was investigated. Above a given pump energy a randomly distributed series of bright tiny spots appear, giving rise to a strongly fluctuating emission pattern. The spectral analysis reveals discrete sharp peaks (about 0.5nm) slightly blueshifted with respect to the highest efficiency region of the gain medium. A comparative study was performed in systems having different sizes and confining geometries, corroborating the idea that the random lasing observed in dye doped nematic phase is fluctuation driven through a recurrent multiple scattering process.
Factors influencing herbicide efficacy when removing lucerne prior to cropping
Authors: Davies S. L. , Storrie A. M. , Cook A. S. , Latta R. A. , Swan A. D. , Peoples M. B.
Published: September 2006

Farmers often experience inconsistent responses when using herbicides to terminate an established lucerne pasture prior to cropping. In an attempt to redress this problem, a series of field experiments were conducted between 1999 and 2002 at various locations in southern and northern New South Wales, the Australian Capital Territory, and south Western Australia that aimed to identify management guidelines that improved the efficacy of herbicide mixtures commonly used to remove lucerne. Collectively, these studies indicated that herbicides were generally less effective when applied either early (less than 2 weeks) or late (6 weeks or more) in the regrowth cycle of lucerne after defoliation. Herbicide efficacy tended to be greatest if applied to regrowth 3–5 weeks after defoliation, which corresponds to a time when the lucerne crown and root reserves are likely to be in the process of being replenished by photoassimilates transported from the shoot. The impact of timing of herbicide application in relation to season was compared at a number of locations. Across all the sites and years, spring herbicide applications were generally the most effective, removing on average 87% of the lucerne (range 53–100%) compared with 72% in summer (24–100%) and 60% in autumn (7–92%). Spring applications were also more consistent in their effect, removing >80% of the lucerne plants in 9 out of 12 experiments, whereas similar rates of removal occurred on 4 occasions in 9 summer applications and only twice in 8 autumn applications. Some of the seasonal variation could be explained by differences in the amount of rainfall prior to herbicide applications. It was assumed that the relationship between rainfall and herbicide efficacy reflected the stimulation of lucerne shoot and root growth by the additional soil moisture before herbicide treatment. Herbicide mixtures that contained ingredients such as picloram that retain residual activity in the soil tended to be more effective and were less influenced by lucerne growth and season than those herbicides with little or no residual activity. However, such chemicals could potentially restrict which crops can subsequently be grown after a lucerne pasture has been removed. It was concluded that >80% of lucerne plants were likely to be removed using herbicides provided that the herbicide treatment was applied to actively growing lucerne 3–5 weeks after defoliation, and when greater than 70–95 mm rain had fallen in the 6–8 weeks prior to application.
Task-modulated “what” and “where” pathways in human auditory cortex
Authors: Ahveninen Jyrki , Jääskeläinen Iiro P. , Raij Tommi , Bonmassar Giorgio , Devore Sasha , Hämäläinen Matti , Levänen Sari , Lin Fa-Hsuan , Sams Mikko , Shinn-Cunningham Barbara G. , Witzel Thomas , Belliveau John W.
Published: September 2006

Human neuroimaging studies suggest that localization and identification of relevant auditory objects are accomplished via parallel parietal-to-lateral-prefrontal “where” and anterior-temporal-to-inferior-frontal “what” pathways, respectively. Using combined hemodynamic (functional MRI) and electromagnetic (magnetoencephalography) measurements, we investigated whether such dual pathways exist already in the human nonprimary auditory cortex, as suggested by animal models, and whether selective attention facilitates sound localization and identification by modulating these pathways in a feature-specific fashion. We found a double dissociation in response adaptation to sound pairs with phonetic vs. spatial sound changes, demonstrating that the human nonprimary auditory cortex indeed processes speech-sound identity and location in parallel anterior “what” (in anterolateral Heschl’s gyrus, anterior superior temporal gyrus, and posterior planum polare) and posterior “where” (in planum temporale and posterior superior temporal gyrus) pathways as early as ≈70–150 ms from stimulus onset. Our data further show that the “where” pathway is activated ≈30 ms earlier than the “what” pathway, possibly enabling the brain to use top-down spatial information in auditory object perception. Notably, selectively attending to phonetic content modulated response adaptation in the “what” pathway, whereas attending to sound location produced analogous effects in the “where” pathway. This finding suggests that selective-attention effects are feature-specific in the human nonprimary auditory cortex and that they arise from enhanced tuning of receptive fields of task-relevant neuronal populations.
Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure
Authors: Bisping Egbert , Ikeda Sadakatsu , Kong Sek Won , Tarnavski Oleg , Bodyak Natalya , McMullen Julie R. , Rajagopal Satish , Son Jennifer K. , Ma Qing , Springer Zhangli , Kang Peter M. , Izumo Seigo , Pu William T.
Published: September 2006

An important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiomyocytes, the transcription factor
Gata4
is required for agonist-induced hypertrophy. We hypothesized that, in the intact organism,
Gata4
is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of
Gata4
(
G4D
). At baseline,
G4D
mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC),
G4D
mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls,
G4D
-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed up-regulation of genes associated with apoptosis and fibrosis, including members of the TGF-β pathway. Our data demonstrate that
Gata4
is essential for cardiac function in the postnatal heart. After pressure overload,
Gata4
regulates the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced failure.
Inhibitors of
Plasmodium falciparum
methionine aminopeptidase 1b possess antimalarial activity
Authors: Chen Xiaochun , Chong Curtis R. , Shi Lirong , Yoshimoto Tadashi , Sullivan David J. , Liu Jun O.
Published: September 2006

With >1 million deaths annually, mostly among children in sub-Saharan Africa, malaria poses one of the most critical challenges in medicine today. Although introduction of the artemisinin class of antimalarial drugs has offered a temporary solution to the problem of drug resistance, new antimalarial drugs are needed to ensure effective control of the disease in the future. Herein, we have investigated members of the methionine aminopeptidase family as potential antimalarial targets. The
Plasmodium falciparum
methionine aminopeptidase 1b (PfMetAP1b), one of four MetAP proteins encoded in the
P. falciparum
genome, was cloned, overexpressed, purified, and used to screen a 175,000-compound library for inhibitors. A family of structurally related inhibitors containing a 2-(2-pyridinyl)-pyrimidine core was identified. Structure/activity studies led to the identification of a potent PfMetAP1b inhibitor, XC11, with an IC
50
of 112 nM. XC11 was highly selective for PfMetAP1b and did not exhibit significant cytotoxicity against primary human fibroblasts. Most importantly, XC11 inhibited the proliferation of
P. falciparum
strains 3D7 [chloroquine (CQ)-sensitive] and Dd2 (multidrug-resistant)
in vitro
and is active in mouse malaria models for both CQ-sensitive and CQ-resistant strains. These results suggest that PfMetAP1b is a promising target and XC11 is an important lead compound for the development of novel antimalarial drugs.
Ex vivo
pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy
Authors: Sasaki Ken-ichiro , Heeschen Christopher , Aicher Alexandra , Ziebart Thomas , Honold Joerg , Urbich Carmen , Rossig Lothar , Koehl Ulrike , Koyanagi Masamichi , Mohamed Annisuddin , Brandes Ralf P. , Martin Hans , Zeiher Andreas M. , Dimmeler Stefanie
Published: September 2006

Bone marrow mononuclear cells (BMC) from patients with ischemic cardiomyopathy (ICMP) show a reduced neovascularization capacity
in vivo
. NO plays an important role in neovascularization, and NO bioavailability is typically reduced in patients with ICMP. We investigated whether the impaired neovascularization capacity of ICMP patient-derived progenitor cells can be restored by pretreatment with the novel endothelial NO synthase (eNOS) transcription enhancer AVE9488 (AVE).
Ex vivo
pretreatment of BMC from patients with ICMP with AVE significantly increased eNOS mRNA expression by 2.1-fold (
P
< 0.05) and eNOS activity as assessed by ESR by >3-fold (
P
< 0.05). The increased eNOS expression was associated with an enhanced migratory capacity
in vitro
(
P
< 0.01) and improved neovascularization capacity of the infused BMC in an ischemic hind limb model
in vivo
(
P
< 0.001). The improvement in ischemic limb perfusion after infusion of AVE-pretreated BMC resulted in an increase in swimming time (
P
< 0.05). The enhancement of limb perfusion by AVE-treated BMC was abrogated by
ex vivo
pretreatment with the eNOS inhibitor N
G
-nitro-
l
-arginine methyl ester. Consistently, AVE showed no effect on the impaired migratory capacity of BMC derived from eNOS-deficient mice, documenting the specific involvement of NO. The reduced neovascularization capacity of BMC from patients with ICMP may limit their therapeutic potential in cell therapy studies. Here, we show that pharmacological enhancement of eNOS expression with AVE at least partially reverses the impaired functional activity of BMC from ICMP patients, highlighting the critical role of NO for progenitor cell function.
Helmholtz decomposition coupling rotational to irrotational flow of a viscous fluid
Authors: Joseph Daniel D.
Published: September 2006

In this work, I present the form of the Navier–Stokes equations implied by the Helmholtz decomposition in which the relation of the irrotational and rotational velocity fields is made explicit. The idea of self-equilibration of irrotational viscous stresses is introduced. The decomposition is constructed by first selecting the irrotational flow compatible with the flow boundaries and other prescribed conditions. The rotational component of velocity is then the difference between the solution of the Navier–Stokes equations and the selected irrotational flow. To satisfy the boundary conditions, the irrotational field is required, and it depends on the viscosity. Five unknown fields are determined by the decomposed form of the Navier–Stokes equations for an incompressible fluid: the rotational component of velocity, the pressure, and the harmonic potential. These five fields may be readily identified in analytic solutions available in the literature. It is clear from these exact solutions that potential flow of a viscous fluid is required to satisfy prescribed conditions, like the no-slip condition at the boundary of a solid or continuity conditions across a two-fluid boundary. It can be said that equations governing the Helmholtz decomposition describe the modification of irrotational flow due to vorticity, but the analysis shows the two fields are coupled and cannot be completely determined independently.
TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity
Authors: Bartolomucci A. , La Corte G. , Possenti R. , Locatelli V. , Rigamonti A. E. , Torsello A. , Bresciani E. , Bulgarelli I. , Rizzi R. , Pavone F. , D’Amato F. R. , Severini C. , Mignogna G. , Giorgi A. , Schininà M. E. , Elia G. , Brancia C. , Ferri G.-L. , Conti R. , Ciani B. , Pascucci T. , Dell’Omo G. , Muller E. E. , Levi A. , Moles A.
Published: September 2006

The
vgf
gene has been identified as an energy homeostasis regulator.
Vgf
encodes a 617-aa precursor protein that is processed to yield an incompletely characterized panel of neuropeptides. Until now, it was an unproved assumption that VGF-derived peptides could regulate metabolism. Here, a VGF peptide designated TLQP-21 was identified in rat brain extracts by means of immunoprecipitation, microcapillary liquid chromatography–tandem MS, and database searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP-21 (15 μg/day for 14 days) increased resting energy expenditure (EE) and rectal temperature in mice. These effects were paralleled by increased epinephrine and up-regulation of brown adipose tissue β2-AR (β2 adrenergic receptor) and white adipose tissue (WAT) PPAR-δ (peroxisome proliferator-activated receptor δ), β3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of locomotor activity and thyroid hormones. Hypothalamic gene expression of orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body and WAT weight as well as hormonal changes that are associated with a high-fat regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its effects by stimulating autonomic activation of adrenal medulla and adipose tissues. In conclusion, we present here the identification in the CNS of a previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v. infusion effected an increase in EE and limited the early phase of diet-induced obesity.
Determining the underlying Fermi surface of strongly correlated superconductors
Authors: Gros Claudius , Edegger Bernhard , Muthukumar V. N. , Anderson P. W.
Published: September 2006

The notion of a Fermi surface (FS) is one of the most ingenious concepts developed by solid-state physicists during the past century. It plays a central role in our understanding of interacting electron systems. Extraordinary efforts have been undertaken, by both experiment and theory, to reveal the FS of the high-temperature superconductors, the most prominent class of strongly correlated superconductors. Here, we discuss some of the prevalent methods used to determine the FS and show that they generally lead to erroneous results close to half-filling and at low temperatures, because of the large superconducting gap (pseudogap) below (above) the superconducting transition temperature. Our findings provide a perspective on the interplay between strong correlations and superconductivity and highlight the importance of strong coupling theories for the characterization and determination of the underlying FS in angle-resolved photoemission spectroscopy experiments.
Genes with internal repeats require the THO complex for transcription
Authors: Voynov Vladimir , Verstrepen Kevin J. , Jansen An , Runner Vanessa M. , Buratowski Stephen , Fink Gerald R.
Published: September 2006

The evolutionarily conserved multisubunit THO complex, which is recruited to actively transcribed genes, is required for the efficient expression of
FLO11
and other yeast genes that have long internal tandem repeats.
FLO11
transcription elongation in Tho
−
mutants is hindered in the region of the tandem repeats, resulting in a loss of function. Moreover, the repeats become genetically unstable in Tho
−
mutants. A
FLO11
gene without the tandem repeats is transcribed equally well in Tho
+
or Tho
−
strains. The Tho
−
defect in transcription is suppressed by overexpression of topoisomerase I, suggesting that the THO complex functions to rectify aberrant structures that arise during transcription.
Continuous up-regulation of heat shock proteins in larvae, but not adults, of a polar insect
Authors: Rinehart Joseph P. , Hayward Scott A. L. , Elnitsky Michael A. , Sandro Luke H. , Lee Richard E. , Denlinger David L.
Published: September 2006

Antarctica's terrestrial environment is a challenge to which very few animals have adapted. The largest, free-living animal to inhabit the continent year-round is a flightless midge,
Belgica antarctica
. Larval midges survive the lengthy austral winter encased in ice, and when the ice melts in summer, the larvae complete their 2-yr life cycle, and the wingless adults form mating aggregations while subjected to surprisingly high substrate temperatures. Here we report a dichotomy in survival strategies exploited by this insect at different stages of its life cycle. Larvae constitutively up-regulate their heat shock proteins (small hsp, hsp70, and hsp90) and maintain a high inherent tolerance to temperature stress. High or low temperature exposure does not further up-regulate these genes nor does it further enhance thermotolerance. Such “preemptive” synthesis of hsps is sufficient to prevent irreversible protein aggregation in response to a variety of common environmental stresses. Conversely, adults exhibit no constitutive up-regulation of their hsps and have a lower intrinsic tolerance to high temperatures, but their hsps can be thermally activated, resulting in enhanced thermotolerance. Thus, the midge larvae, but not the adults, have adopted the unusual strategy of expressing hsps continuously, possibly to facilitate proper protein folding in a cold habitat that is more thermally stable than that of the adults but a habitat subjected frequently to freeze-thaw episodes and bouts of pH, anoxic, and osmotic stress.
Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin
Authors: Ma Peisong , Beck Shannon L. , Raab Ronald W. , McKown Robert L. , Coffman George L. , Utani Atsushi , Chirico William J. , Rapraeger Alan C. , Laurie Gordon W.
Published: September 2006

Cell surface heparan sulfate (HS) proteoglycans are carbohydrate-rich regulators of cell migratory, mitogenic, secretory, and inflammatory activity that bind and present soluble heparin-binding growth factors (e.g., fibroblast growth factor, Wnt, Hh, transforming growth factor β, amphiregulin, and hepatocyte growth factor) to their respective signaling receptors. We demonstrate that the deglycanated core protein of syndecan-1 (SDC1) and not HS chains nor SDC2 or -4, appears to target the epithelial selective prosecretory mitogen lacritin. An important and novel step in this mechanism is that binding necessitates prior partial or complete removal of HS chains by endogenous heparanase. This limits lacritin activity to sites where heparanase appears to predominate, such as sites of exocrine cell migration, secretion, renewal, and inflammation. Binding is mutually specified by lacritin's C-terminal mitogenic domain and SDC1's N terminus. Heparanase modification of the latter transforms a widely expressed HS proteoglycan into a highly selective surface-binding protein. This novel example of cell specification through extracellular modification of an HS proteoglycan has broad implications in development, homeostasis, and disease.
Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA
Authors: Poncet Delphine , Pauleau Anne-Laure , Szabadkai Gyorgy , Vozza Angelo , Scholz Sebastian R. , Le Bras Morgane , Brière Jean-Jacques , Jalil Abdelali , Le Moigne Ronan , Brenner Catherine , Hahn Gabriele , Wittig Ilka , Schägger Hermann , Lemaire Christophe , Bianchi Katiuscia , Souquère Sylvie , Pierron Gerard , Rustin Pierre , Goldmacher Victor S. , Rizzuto Rosario , Palmieri Ferdinando , Kroemer Guido
Published: September 2006

Replication of human cytomegalovirus (CMV) requires the expression of the viral mitochondria–localized inhibitor of apoptosis (vMIA). vMIA inhibits apoptosis by recruiting Bax to mitochondria, resulting in its neutralization. We show that vMIA decreases cell size, reduces actin polymerization, and induces cell rounding. As compared with vMIA-expressing CMV, vMIA-deficient CMV, which replicates in fibroblasts expressing the adenoviral apoptosis suppressor E1B19K, induces less cytopathic effects. These vMIA effects can be separated from its cell death–inhibitory function because vMIA modulates cellular morphology in Bax-deficient cells. Expression of vMIA coincided with a reduction in the cellular adenosine triphosphate (ATP) level. vMIA selectively inhibited one component of the ATP synthasome, namely, the mitochondrial phosphate carrier. Exposure of cells to inhibitors of oxidative phosphorylation produced similar effects, such as an ATP level reduced by 30%, smaller cell size, and deficient actin polymerization. Similarly, knockdown of the phosphate carrier reduced cell size. Our data suggest that the cytopathic effect of CMV can be explained by vMIA effects on mitochondrial bioenergetics.
Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases
Authors: Gadola Stephan D. , Silk Jonathan D. , Jeans Aruna , Illarionov Petr A. , Salio Mariolina , Besra Gurdyal S. , Dwek Raymond , Butters Terry D. , Platt Frances M. , Cerundolo Vincenzo
Published: September 2006

Glycolipid ligands for invariant natural killer T cells (iNKT cells) are loaded onto CD1d molecules in the late endosome/lysosome. Accumulation of glycosphingolipids (GSLs) in lysosomal storage diseases could potentially influence endogenous and exogenous lipid loading and/or presentation and, thus, affect iNKT cell selection or function. The percentages and frequency of iNKT cells were reduced in multiple mouse models of lysosomal GSL storage disease, irrespective of the specific genetic defect or lipid species stored. Reduced numbers of iNKT cells resulted in the absence of cytokine production in response to α-galactosylceramide (α-GalCer) and reduced iNKT cell–mediated lysis of wild-type targets loaded with α-GalCer. The reduction in iNKT cells did not result from defective expression of CD1d or a lack of antigen-presenting cells. Although H-2 restricted CD4+ T cell responses were generally unaffected, processing of a lysosome-dependent analogue of α-GalCer was impaired in all the strains of mice tested. These data suggest that GSL storage may result in alterations in thymic selection of iNKT cells caused by impaired presentation of selecting ligands.
Clearcut: a fast implementation of relaxed neighbor joining
Authors: Sheneman Luke , Evans Jason , Foster James A.
Published: September 2006

Summary: Clearcut is an open source implementation for the relaxed neighbor joining (RNJ) algorithm. While traditional neighbor joining (NJ) remains a popular method for distance-based phylogenetic tree reconstruction, it suffers from a O(N3) time complexity, where N represents the number of taxa in the input. Due to this steep asymptotic time complexity, NJ cannot reasonably handle very large datasets. In contrast, RNJ realizes a typical-case time complexity on the order of N2logN without any significant qualitative difference in output. RNJ is particularly useful when inferring a very large tree or a large number of trees. In addition, RNJ retains the desirable property that it will always reconstruct the true tree given a matrix of additive pairwise distances. Clearcut implements RNJ as a C program, which takes either a set of aligned sequences or a pre-computed distance matrix as input and produces a phylogenetic tree. Alternatively, Clearcut can reconstruct phylogenies using an extremely fast standard NJ implementation.

Availability: Clearcut source code is available for download at:

Contact:  sheneman@hungry.com

Supplementary information:
ADAM: another database of abbreviations in MEDLINE
Authors: Zhou Wei , Torvik Vetle I. , Smalheiser Neil R.
Published: September 2006

Motivation: Abbreviations are an important type of terminology in the biomedical domain. Although several groups have already created databases of biomedical abbreviations, these are either not public, or are not comprehensive, or focus exclusively on acronym-type abbreviations. We have created another abbreviation database, ADAM, which covers commonly used abbreviations and their definitions (or long-forms) within MEDLINE titles and abstracts, including both acronym and non-acronym abbreviations.

Results: A model of recognizing abbreviations and their long-forms from titles and abstracts of MEDLINE (2006 baseline) was employed. After grouping morphological variants, 59 405 abbreviation/long-form pairs were identified. ADAM shows high precision (97.4%) and includes most of the frequently used abbreviations contained in the Unified Medical Language System (UMLS) Lexicon and the Stanford Abbreviation Database. Conversely, one-third of abbreviations in ADAM are novel insofar as they are not included in either database. About 19% of the novel abbreviations are non-acronym-type and these cover at least seven different types of short-form/long-form pairs.

Availability: A free, public query interface to ADAM is available at , and the entire database can be downloaded as a text file.

Contact: neils@uic.edu
Reconstructing contiguous regions of an ancestral genome
Authors: Ma Jian , Zhang Louxin , Suh Bernard B. , Raney Brian J. , Burhans Richard C. , Kent W. James , Blanchette Mathieu , Haussler David , Miller Webb
Published: September 2006

This article analyzes mammalian genome rearrangements at higher resolution than has been published to date. We identify 3171 intervals, covering ∼92% of the human genome, within which we find no rearrangements larger than 50 kilobases (kb) in the lineages leading to human, mouse, rat, and dog from their most recent common ancestor. Combining intervals that are adjacent in all contemporary species produces 1338 segments that may contain large insertions or deletions but that are free of chromosome fissions or fusions as well as inversions or translocations >50 kb in length. We describe a new method for predicting the ancestral order and orientation of those intervals from their observed adjacencies in modern species. We combine the results from this method with data from chromosome painting experiments to produce a map of an early mammalian genome that accounts for 96.8% of the available human genome sequence data. The precision is further increased by mapping inversions as small as 31 bp. Analysis of the predicted evolutionary breakpoints in the human lineage confirms certain published observations but disagrees with others. Although only a few mammalian genomes are currently sequenced to high precision, our theoretical analyses and computer simulations indicate that our results are reasonably accurate and that they will become highly accurate in the foreseeable future. Our methods were developed as part of a project to reconstruct the genome sequence of the last ancestor of human, dogs, and most other placental mammals.
The phylogeny of the living and fossil Sphenisciformes (penguins)
Authors: Ksepka Daniel T. , Bertelli Sara , Giannini Norberto P.
Published: September 2006

We present the first phylogenetic analysis of the Sphenisciformes that extensively samples fossil taxa. Combined analysis of 181 morphological characters and sequence fragments from mitochondrial and nuclear genes (12S, 16S, COI, cytochrome b, RAG‐1) yields a largely resolved tree. Two species of the New Zealand Waimanu form a trichotomy with all other penguins in our result. The much discussed giant penguins Anthropornis and Pachydyptes are placed in two clades near the base of the tree. Stratigraphic and phylogenetic evidence suggest that some lineages of penguins attained very large body size rapidly and early in the clade's evolutionary history. The only fossil taxa that fall inside the crown clade Spheniscidae are fossil species assigned to the genus Spheniscus. Thus, extant penguin diversity is more accurately viewed as the product of a successful radiation of derived taxa than as an assemblage of survivors belonging to numerous lineages. The success of the Spheniscidae may be due to novel feeding adaptations and a more derived flipper apparatus. We offer a biogeographical scenario for penguins that incorporates fossil distributions and paleogeographic reconstructions of the Southern continent's positions. Our results do not support an expansion of the Spheniscidae from a cooling Continental Antarctica, but instead suggest those species that currently breed in that area are the descendants of colonizers from the Subantarctic. Many important divergence events in the clade Spheniscidae can instead be explained by dispersal along the paths of major ocean currents and the emergence of new islands due to tectonic events.

© The Willi Hennig Society 2006.
Adrenal axis suppression unrelated to the dynamics of dosing with beclomethasone monopropionate
Authors: Mulrennan Siobhan A. , Hogg Joseph S. , Teoh Richard C. , Morice Alyn H.
Published: September 2006

Aims

Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment. At high doses they can give rise to systemic side‐effects such as hypothalamic‐pituitary‐adrenal (HPA) axis suppression. This effect may depend on the delivery system, which in turn alters drug deposition and adsorption. We hypothesized that adrenal suppression depends on the rate of steroid absorption rather than the total steroid dose received.

Methods

Eight healthy adult males were recruited for a randomized double‐blind placebo controlled trial. Adrenocortical suppression ability was demonstrated by a 30% suppression of early morning cortisol following 1 mg dexamethasone. Subjects then attended in the evening on two occasions receiving 500 µg of intravenous beclomethasone monopropionate (17‐BMP) for either 15 min or 2 h. Overnight urinary cortisol : creatinine (C : C) ratio was measured before and after the infusion and an 08.00 h serum cortisol was measured following the infusion.

Results

Mean C : C pre and post 15 min infusion was 5.97 and 3.22 (P = 0.005). Mean C : C pre and post 2 h infusion was 6.31 and 4.15 (P = 0.004). Delta C : C and mean 08.00 h cortisol for 15 min and 2 h infusion was 2.74 and 2.16 and 425 nmol l−1 and 400 nmol l−1, respectively (P = NS).

Conclusions

The rate of infusion of 17‐BMP seemed to have little effect on the degree of adrenal suppression. Individual C : C ratios were reproducible. Differences in absorption of ICS are unlikely to explain observed differences in HPA axis suppression.
Differential protein binding of indinavir and saquinavir in matched maternal and umbilical cord plasma
Authors: Sudhakaran Sreeja , Rayner Craig R. , Li Jian , Kong David C. M. , Gude Neil M. , Nation Roger L.
Published: September 2006

Aims

To determine whether lower umbilical cord than maternal binding of indinavir and saquinavir contributed to the low cord : maternal (C : M) total concentration ratios reported previously.

Methods

Indinavir and saquinavir unbound fraction (fu) was determined using equilibrium dialysis. Buffer solutions of human serum albumin (HSA) (20.0, 30.0, 40.0 g l−1) and α1‐acid glycoprotein (AAG) (0.20, 0.60, 2.00 g l−1) were spiked with indinavir (1.00 and 8.00 mg l−1) or saquinavir (0.15 and 1.50 mg l−1). Matched maternal and umbilical cord plasma was spiked with 1.00 mg l−1 indinavir (n = 12) or 0.15 mg l−1 saquinavir (n = 20). Spiked protein/plasma solutions were dialyzed against isotonic phosphate buffer, at 37 °C. At equilibrium, indinavir and saquinavir concentrations were quantified, and the fu determined.

Results

Indinavir and saquinavir demonstrated protein concentration‐dependent binding in buffer solutions of HSA and AAG. Indinavir fu was significantly higher in umbilical cord (0.53 ± 0.12) compared with maternal (0.36 ± 0.11) plasma (95% CI of the difference −0.26, −0.097). Similarly, saquinavir fu was different between umbilical cord (0.0090 ± 0.0046) and maternal plasma (0.0066 ± 0.0039) (95% CI of the difference −0.0032, −0.0016). The transplacental AAG concentration gradient contributed significantly to the binding differential of both drugs.

Conclusions

The differential plasma binding of both drugs, which was largely the result of the transplacental AAG concentration gradient, would contribute to the low C : M total plasma concentration ratios observed previously. Unbound concentrations of indinavir and saquinavir are likely to be substantially lower in umbilical cord than maternal plasma.
Distribution of the FcγRIIIa 176 F/V polymorphism amongst healthy Chinese, Malays and Asian Indians in Singapore
Authors: Chong K. T. , Ho W. F. , Koo S. H. , Thompson Peter , Lee Edmund J. D.
Published: September 2006

What is already known about this subject

• Genetic variability of the FcγRIIIa 176 F/V polymorphism has been widely studied in patients with systemic lupus erythomatosus and rheumatoid arthritis, as well as the general population of various White groups.

• Its implications in disease pathogenesis and response to therapeutics have been well documented.

• This study aimed to profile its polymorphism pattern in the Asian population, thus it serves as useful reference controls in disease association studies and tailoring therapy to ethnic‐specific populations.

What this study adds

• In this study, we have established the genetic variability profile of the FcγRIIIa 176 F/V polymorphism in three distinct Asian groups (Chinese, Malays and Indians) and also supplemented existing data based on ethnic‐specific healthy controls.

• The polymorphism pattern of Malays was found to differ significantly from Chinese and Indians, which was also extended to almost all other healthy controls of various ethnic groups published elsewhere.

• Such differences could have implications in disease susceptibility and pathogenesis, as well as response to drug therapeutics.

Aims

To determine and compare the distribution of the FcγRIIIa 176 F/V polymorphism across three ethnically distinct populations (Chinese, Asian Indians and Malays) in Singapore.

Methods

The FcγRIIIa 176 F/V polymorphism was genotyped by direct sequencing from genomic DNA samples obtained from normal healthy Chinese, Asian Indians and Malays (n = 192 from each population).

Results

The allelic frequencies of the high binding affinity FcγRIIIa 176 V allele for Chinese, Asian Indians and Malays were 35%, 33% and 46%, respectively (F allele frequencies were 65%, 67% and 54%, respectively). Genotype distributions were found to conform to the Hardy–Weinberg law (P > 0.05) in each group. χ2 comparisons revealed significant differences in the genotype distributions of the FcγRIIIa 176 V/F polymorphism of Malays from the other two populations (Chinese and Asian Indians). However, no significant difference in the genotype distributions of the FcγRIIIa 176 V/F polymorphism was observed between Chinese and Asian Indian populations.

Conclusions

The genotype distributions of the FcγRIIIa 176 V/F polymorphism in healthy Malays are significantly different from both Chinese and Indians. These observations provide the fundamentals on which future disease associations may be built and also present important implications for the design of therapeutic regimens amongst various ethnic groups.
Development of autologous cytotoxic CD4+ T clones in a human model of B‐cell non‐Hodgkin follicular lymphoma
Authors: Mi Jian‐Qing , Manches Olivier , Wang Jin , Perron Pascal , Weisbuch Sébastien , Marche Patrice N. , Renversez Jean‐Charles , Bensa Jean‐Claude , Sotto Jean‐Jacques , Cahn Jean‐Yves , Leroux Dominique , Bonnefoix Thierry
Published: September 2006

Immunotherapy for cancer aims to generate cytotoxic cells that are capable of eradicating tumour cells. It has been well demonstrated that helper, non‐cytotoxic CD4+ T cells are important for the induction and maintenance of anti‐tumour immunity exerted by cytotoxic CD8+ T cells. In contrast, the existence of direct anti‐tumour, effector cytotoxic CD4+ T cells remains elusive, mainly due to the paucity of reliable experimental data, especially in human B‐cell non‐Hodgkin lymphomas. This study developed an appropriate, autologous follicular B‐cell non‐Hodgkin follicular lymphoma model, including the in vitro establishment of a malignant, human leucocyte antigen class I (HLA‐I) deficient B‐cell line, and the generation of three autologous anti‐tumour cytotoxic CD4+ T‐cell clones originating from the peripheral blood of the same patient. These three clones were considered as tumour specific, because they were capable of killing the malignant, HLA‐I‐deficient B‐cell line through a classical HLA‐II restricted perforin‐mediated pathway, but did not lyse the Epstein–Barr virus‐infected autologous normal B lymphocytes. All three CD4+clones were T‐cell receptor Vβ17‐Dβ1‐Jβ1·2 and exhibited an identical complementarity‐determining region 3, suggesting the immunodominance of a single peptide antigen presented by tumour cells. Such lymphoma models would provide a useful tool for in vivo expansion and the adoptive transfer of selected CD4+ cytotoxic cells in immunotherapeutic strategies.
Effects of elevated pCO2 on epilithic and endolithic metabolism of reef carbonates
Authors: ALINE TRIBOLLET , ATKINSON M. J. , CHRISTOPHER LANGDON
Published: September 2006

We investigated effects of elevated partial pressure of CO2 (pCO2) on the metabolism of epilithic and endolithic phototrophic communities that colonized experimental coral blocks. Blocks of the massive coral Porites lobata were exposed to colonization by epilithic and endolithic organisms at an oceanic site in Kaneohe Bay (Hawaii) for 6 months, and then were transported to laboratory tanks. A bubbling system was used to maintain two treatments for 3 months, one at ambient pCO2 (400 ppm) and the second at elevated pCO2 (750 ppm). Net photosynthetic rates of epilithic communities in the high pCO2 treatment, dominated by encrusting coralline algae, decreased by 35% while respiration rates remained constant. In contrast, metabolism of endolithic phototrophs, comprised of cyanobacteria and algae, was not significantly affected by the elevated pCO2 even though endoliths contributed about 63% to block production.
Paediatric intraoral mucoepidermoid carcinoma mimicking a bone lesion
Authors: MORAES PAULO , PEREIRA CLAUDIO , ALMEIDA OSLEI , PEREZ DANYEL , CORREA MARIA ELVIRA , ALVES FABIO
Published: September 2006

Background.  Mucoepidermoid carcinoma of the salivary glands occurs most frequently in adults during the fifth and sixth decades of life. Although uncommon, it is the main malignant salivary gland tumour in children, particularly adolescents.

Case report.  A 14‐year‐old girl presented with a mass in her palate that had had a duration of one year. On panoramic X‐ray, a well‐delimited radiolucent area was observed on the left maxillary sinus region. The initial clinical diagnostic hypothesis was that this was a central giant cell granuloma. An incisional biopsy was performed and the final microscopic diagnosis was mucoepidermoid carcinoma. The tumour was removed by a wide transoral resection and the patient has been asymptomatic for 4 years.

Conclusion.  Mucoepidermoid carcinoma in paediatric patients is uncommon, but it must be considered in differential diagnoses of intraoral submucosal mass/nodules in children, particularly in the palate.
Plasmacytoid myoepithelioma of the palate in a child
Authors: PEREZ DANYEL ELIAS da CRUZ , LOPES MÁRCIO AJUDARTE , ALMEIDA OSLEI PAES de , JORGE JACKS , KOWALSKI LUIZ PAULO
Published: September 2006

Background.  Myoepithelioma is a rare benign salivary gland tumour, localized most frequently in the parotid and in minor intraoral salivary glands. There have been only four cases of myoepithelioma in children and adolescents reported in the English‐language literature, all of them involving the plasmacytoid variant.

Case Report.  A 13‐year‐old boy, complained of a painless nodule of the palate. Incisional biopsy was performed and revealed large plasmacytoid cells with a round and eccentric nuclei. The diagnosis was consistent with myoepithelioma, plasmocytoid variant. Tumour cells were positive for cytokeratins, vimentin and S‐100 protein. Surgical resection was performed and no evidences of tumour recurrence were observed after 6 years of the treatment.

Conclusion.  Myoepithelioma is a very rare tumour in children and apparently presents a good prognosis, similar to occur in adult patients.
A community model of group therapy for the older patients with chronic obstructive pulmonary disease: a pilot study
Authors: Woo Jean , Chan Wayne , Yeung Fai , Chan Wai M. , Hui Elsie , Lum Christopher M. , Or Kevin H. , Hui David S. C. , Lee Diana T. F.
Published: September 2006

Objective  A community‐based programme for chronic obstructive pulmonary disease (COPD) patients in group sessions is designed, and the feasibility, acceptability and physical and psychosocial outcomes evaluated.

Methods  Patients with COPD discharged from hospital, or those attending specialist outpatient clinic, with a history of hospital admission owing to COPD in the preceding 12 months were recruited. Those who had malignancy or were housebound were excluded. Group sessions were arranged once a week in a Community Centre, and consisted of two hourly sessions. The components of each session consist of education regarding the disease, breathing techniques, use of oxygen and other medication, smoking cessation, nutrition, dyspnoea management skills, relaxation and energy conservation techniques, introduction of social and community support, and strengthening as well as aerobic exercises. Assessments before and after intervention include lung function, 6 minutes walk test (6MWT), general Health Questionnaire (GHQ), the St. George’s Respiratory Questionnaire (SGRQ), and a COPD knowledge Questionnaire. A programme evaluation was carried out using questionnaire and group discussions.

Results  Forty‐four subjects were recruited, with 75% completing the programme, and 20% with drawing for unavoidable reasons. Statistically significant improvement was noted in all domains of the GHQ, SGRQ, and knowledge test, while the mean 6MWT improved, although statistical significance was not reached. Subjects were enthusiastic about the provision of this service in helping them cope with the disease through empowerment and mutual support.

Conclusion  A group community intervention programme for COPD patients is feasible and acceptable, with positive psychosocial outcomes. Such a model could be further developed and cost‐effectiveness evaluated as a model of chronic disease management in the community.