bluuebunny/crossref_metadata_2025 huggingface dataset:
FETOSCOPIC SURGERY FOR IN-UTERO MANAGEMENT OF CONGENITAL DIAPHRAGMATIC HERNIA
Authors: NELSON SCOTT M , CAMERON ALAN D , DEPREST JAN A
Published: April 2006

Until recently two possibilities were available to the expectant parents of a fetus diagnosed with a congenital diaphragmatic hernia: termination of pregnancy or continuation of the pregnancy until term with a potential change in the place of delivery. Open fetal surgery has been used to treat a growing number of congenital malformations with life-threatening or highly morbid consequences including congenital diaphragmatic hernia. However, its effectiveness is limited by the occurrence of preterm labour, chorioamniotic membrane separation, preterm prelabour rupture of the membranes and altered fetal homeostasis. These problems were the impetus for the development of minimal access fetal surgery. Developments in endoscopic surgical technology over the past three decades have provided the opportunity to develop techniques adapted for prenatal fetal intervention.
Trace element composition of mantle end‐members: Implications for recycling of oceanic and upper and lower continental crust
Authors: Willbold Matthias , Stracke Andreas
Published: April 2006

Recycling of oceanic crust together with different types of marine sediments has become somewhat of a paradigm for explaining the chemical and isotopic composition of ocean island basalts. New high‐precision trace element data on samples from St. Helena, Gough, and Tristan da Cunha, in addition to recent data from the literature, show that the trace element and isotope systematics in enriched mantle (EM) basalts are more complex than previously thought. EM basalts have some common characteristics (e.g., high Rb/La, Ba/La, Th/U, and Rb/Sr and low Nb/La and U/Pb) that distinguish them from HIMU basalts (high μ = 238U/204Pb). The isotopically distinct EM‐1 and EM‐2 basalts, however, cannot be clearly distinguished on the basis of incompatible trace element ratios. Ultimately, each suite of EM basalts carries its own specific trace element signature that must reflect different source compositions. In contrast, HIMU basalts show remarkably uniform trace element ratios, with a characteristic depletion in incompatible trace elements (Rb, Ba, Th, U, and Pb) and enrichment in Nb and Ta relative to EM basalts. Compositional similarities between HIMU and EM basalts (e.g., Nb/U, La/Sm, La/Th, Sr/Nd, Ba/K, and Rb/K) suggest that their sources share a common precursor, most likely recycled oceanic lithosphere. The compositional differences between HIMU and EM basalts, on the other hand, can only be explained if the EM sources contain an additional heterogeneous component. Parent‐daughter ratios in subducted marine sediments have a unimodal distribution. Recycling of sediments alone can therefore not account for the isotopic bimodality of EM basalts. The upper and lower continental crust have similarly variable trace elements ratios but are systematically distinct in their Rb/Sr, U/Pb, Th/Pb, and Th/U ratios. Thus the upper and lower continental crust evolve along two distinct isotopic evolution paths but retain their complex trace element characteristics, similar to what is observed in EM basalts. We therefore propose that recycling of oceanic lithosphere together with variable proportions of lower and upper continental crust, which are introduced into the mantle together with the oceanic lithosphere via subduction erosion and/or subduction of marine sediments, respectively, provides a plausible explanation for the trace element and isotope systematics in ocean island basalts.
The Cleft revealed: Geologic, magnetic, and morphologic evidence for construction of upper oceanic crust along the southern Juan de Fuca Ridge
Authors: Stakes Debra S. , Perfit Michael R. , Tivey Maurice A. , Caress David W. , Ramirez Tony M. , Maher Norman
Published: April 2006

The geology and structure of the Cleft Segment of the Southern Juan de Fuca Ridge (JdFR) have been examined using high‐resolution mapping systems, observations by remotely operated vehicle (ROV), ROV‐mounted magnetometer, and the geochemical analysis of recovered lavas. Bathymetric mapping using multibeam (EM300) coupled with in situ observations that focused on near‐axis and flank regions provides a detailed picture of 0 to 400 ka upper crust created at the southern terminus of the JdFR. A total of 53 rock cores and 276 precisely located rock or glass samples were collected during three cruises that included sixteen ROV dives. Our observations of the seafloor during these dives suggest that many of the unfaulted and extensive lava flows that comprise and/or cap the prominent ridges that flank the axial valley emanate from ridge parallel faults and fissures that formed in the highly tectonized zone that forms the walls of the axial valley. The geochemically evolved and heterogeneous nature of these near‐axis and flank eruptions is consistent with an origin within the cooler distal edges of a crustal magma chamber or mush zone. In contrast, the most recent axial eruptions are more primitive (higher MgO), chemically homogeneous lobate, sheet, and massive flows that generate a distinct magnetic high over the axial valley. We suggest that the syntectonic capping volcanics observed off‐axis were erupted from near‐axis and flank fissures and created a thickened extrusive layer as suggested by the magnetic and seismic data. This model suggests that many of the lavas that comprise the elevated ridges that bound the axial valley of the Cleft Segment were erupted during the collapse of a magmatic cycle not during the robust phase that established a new magmatic cycle.
Thermospheric meridional wind control of equatorial spread F and evening prereversal electric field
Authors: Abdu M. A. , Iyer K. N. , de Medeiros R. T. , Batista I. S. , Sobral J. H. A.
Published: April 2006

The role of the evening prereversal zonal electric field enhancement (PRE) as conducive to equatorial spread F (ESF)/plasma bubble development versus that of the magnetic meridional wind as a suppressing factor is examined using digital ionosonde data from an equatorial site, Sao Luis (SL), and a low latitude site, Cachoeira Paulista (CP) in Brazil. The evening vertical plasma drift (Vz) over SL is used, together with the F layer peak height (hmF2) over CP, to compute the magnetic meridional wind. The analysis performed for two epochs, that is, March‐April of 1999 and 2001, provide consistent evidence that the magnetic meridional wind can negatively influence the ESF development in two ways: (a) by reduced development of the PRE and. (b) by direct suppression of the bubble growth
Planetary wave oscillations in mesospheric winds, equatorial evening prereversal electric field and spread F
Authors: Abdu M. A. , Batista P. P. , Batista I. S. , Brum C. G. M. , Carrasco A. J. , Reinisch B. W.
Published: April 2006

Analysis of the MLT region winds measured by a meteor radar and the evening F region vertical plasma drift (prereversal zonal electric field ‐PRE) measured by digisondes over low latitude sites in Brazil, provide evidence of planetary wave (PW) scale oscillations of episodic nature simultaneously at mesospheric and F region heights. ∼4‐day and 7‐day periods are found to dominate the event analyzed. The PW scale oscillations in the PRE produces strong modulation in the equatorial spread F (ESF) irregularity processes as diagnosed by the digisondes. Considerations on the PRE development mechanism involving the E layer integrated conductivity including the effect of metallic ions and tidal winds point to the source of the PRE oscillations to be PW modulation of E region tidal winds. The PW oscillations in PRE appear to be an important source of the day‐to‐day variability in the ESF.
ENSO‐driven carbon see saw in the Indo‐Pacific
Authors: Rixen Tim , Ittekkot Venugopalan , Herunadi Bambang , Wetzel Patrick , Maier‐Reimer E. , Gaye‐Haake Birgit
Published: April 2006

The sediment trap experiments have been carried out during the 2001/2002 El Niño/La Niña transition in the monsoon‐driven and freshwater influenced upwelling system off South Java. The results indicate that enhanced precipitation rates and associated river discharges increase the CO2‐uptake of the biological pump by increasing the organic carbon export and reducing the carbonate precipitation. The freshwater, furthermore, forms a buoyant low salinity surface layer that caps off the nutrient and CO2‐rich subsurface waters which shortens the upwelling season during wet La Niña conditions. A reduced capping‐effect during dryer El Niño conditions strengthens the upwelling and as shown by our model results increase CO2 emission into the atmosphere along the freshwater influenced continental margins in SE Asia. By contrast El Niño weakens upwelling and reduces the CO2 emission in the equatorial Pacific Ocean.
Is there a northern Lesser Antilles forearc block?
Authors: López A. M. , Stein S. , Dixon T. , Sella G. , Calais E. , Jansma P. , Weber J. , LaFemina P.
Published: April 2006

A systematic discrepancy exists between slip vectors of thrust fault earthquakes at the Lesser Antilles trench (LAT) and the predicted direction of North American‐Caribbean convergence. A possibility has been that the discrepancy resulted because neither was well constrained. Estimating Caribbean motion has been challenging owing to the limited data along the plate's complex boundaries. Similarly, earlier studies had few slip vectors because interplate thrust events are infrequent. To address these difficulties, we estimate a new Caribbean‐North America Euler vector using recently available GPS data from sites in the presumably stable interior of the Caribbean, and compare the predicted velocities to a larger set of slip vectors. The discrepancy persists, suggesting the northern Lesser Antilles forearc (NLAF) moves as a distinct entity from both the Caribbean and North America. For simplicity, we treat its motion as a coherent block, but because GPS sites are not within the NLAF, distributed deformation is also possible. Although there is no geologic evidence for the boundaries of the presumed NLAF block, GPS data show that the motions of Martinique, Barbados, and Trinidad are similar to that of the Caribbean, suggesting that none are on the NLAF block, and the southern LAT is weakly coupled.
Temporal evolution of a staircase ion signature observed by Cluster in the mid‐altitude polar cusp
Authors: Escoubet C. P. , Bosqued J. M. , Berchem J. , Trattner K. J. , Taylor M. G. G. T. , Pitout F. , Laakso H. , Masson A. , Dunlop M. , Reme H. , Dandouras I. , Fazakerley A.
Published: April 2006

We use the Cluster string of pearls configuration to investigate temporal variations of ion precipitation in the mid‐altitude polar cusp. On 7 Aug. 2004, Cluster 4 was moving poleward through the Northern cusp, followed by Cluster 1, Cluster 2, and finally Cluster 3. The Wind spacecraft detected a Southward turning of the Interplanetary Magnetic Field (IMF) at the beginning of the cusp crossings and IMF‐Bz stayed negative throughout. Cluster 4 observed a high energy step in the ion dispersion around 1 keV on the equatorward side of the cusp. C1, entering the cusp around 1 minute later, did not observe the high energy step anymore but a partial dispersion with a low energy cut‐off reaching 100 eV. About 9 min later, C3 entered the cusp and observed a full ion dispersion from a few keV down to around 50 eV. The open‐closed boundary, identified by electron precipitation, was initially moving equatorward at a rate of −0.43° ILAT/minute at the beginning of the event and then slowed down to −0.16° ILAT/minute, suggesting the erosion of the dayside magnetosphere under IMF Southward. This event is explained by the onset of dayside reconnection when the IMF turned southward; the step being the first signature of the reconnection that would then evolve as a full dispersion as reconnection goes on. We observed 1–3 keV ions near the open‐closed boundary on the three spacecraft crossings that suggests a continuous reconnection during about 9 minutes.
Limits on the complexity of empirical models of magnetic storm phenomena
Authors: O'Brien T. P.
Published: April 2006

We explore the statistical limits on the complexity of data‐derived models of magnetic storm phenomena, including magnetic indices, plasmapause evolution, and outer radiation belt dynamics. Specifically, we estimate the limits on the number of free parameters justifiable by application of Occam's razor, or the rule of parsimony. These limits arise from the strong intercorrelation of geomagnetic phenomena, which decimates the effective sample size of independent observations of magnetic storm phenomena. We show that the resulting paucity of distinct magnetic storms over the history of magnetic indices and satellite observations severely limits the justifiable complexity of data‐derived models. Our analysis applies to a wide variety of models with a finite number of constant free parameters but not to models with time‐varying parameters nor to nearest‐neighbors models.
MITF mediates cAMP-induced protein kinase C-β expression in human melanocytes
Authors: Park Hee-Young , Wu Christina , Yonemoto Laurie , Murphy-Smith Melissa , Wu Heng , Stachur Christina M. , Gilchrest Barbara A.
Published: April 2006

The cAMP-dependent pathway up-regulates MITF (microphthalmia-associated transcription factor), important for key melanogenic proteins such as tyrosinase, TRP-1 (tyrosinase-related protein 1) and TRP-2. We asked whether MITF is also a key transcription factor for PKC-β (protein kinase C-β), required to phosphorylate otherwise inactive tyrosinase. When paired cultures of human melanocytes were treated with isobutylmethylxanthine, known to increase intracellular cAMP, both protein and mRNA levels of PKC-β were induced by 24 h. To determine whether MITF modulates PKC-β expression, paired cultures of human melanocytes were transfected with dn-MITF (dominant-negative MITF) or empty control vector. By immunoblotting, PKC-β protein was reduced by 63±3.7% within 48 h. Co-transfection of an expression vector for MITF-M, the MITF isoform specific for pigment cells, or empty control vector with a full-length PKC-β promoter–CAT (chloramphenicol acetyltransferase) reporter construct (PKC-β/CAT) into Cos-7 cells showed >60-fold increase in CAT activity. Melanocytes abundantly also expressed MITF-A, as well as the MITF-B and MITF-H isoforms. However, in contrast with MITF-M, MITF-A failed to transactivate co-expressed PKC-β/CAT or CAT constructs under the control of a full-length tyrosinase promoter. Together, these results demonstrate that MITF, specifically MITF-M, is a key transcription factor for PKC-β, linking the PKC- and cAMP-dependent pathways in regulation of melanogenesis.
Two glucose/xylose transporter genes from the yeast Candida intermedia: first molecular characterization of a yeast xylose–H+ symporter
Authors: Leandro Maria José , Gonçalves Paula , Spencer-Martins Isabel
Published: April 2006

Candida intermedia PYCC 4715 was previously shown to grow well on xylose and to transport this sugar by two different transport systems: high-capacity and low-affinity facilitated diffusion and a high-affinity xylose–proton symporter, both of which accept glucose as a substrate. Here we report the isolation of genes encoding both transporters, designated GXF1 (glucose/xylose facilitator 1) and GXS1 (glucose/xylose symporter 1) respectively. Although GXF1 was isolated by functional complementation of an HXT-null (where Hxt refers to hexose transporters) Saccharomyces cerevisiae strain, isolation of the GXS1 cDNA required partial purification and micro-sequencing of the transporter, identified by its relative abundance in cells grown on low xylose concentrations. Both genes were expressed in S. cerevisiae and the kinetic parameters of glucose and xylose transport were determined. Gxs1 is the first yeast xylose/glucose–H+ symporter to be characterized at the molecular level. Comparison of its amino acid sequence with available sequence data revealed the existence of a family of putative monosaccharide–H+ symporters encompassing proteins from several yeasts and filamentous fungi.
Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene
Authors: Vollrath Valeska , Wielandt Ana M. , Iruretagoyena Mirentxu , Chianale Jose
Published: April 2006

The Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) transcription factor regulates gene expression of the GCLC (glutamate–cysteine ligase catalytic subunit), which is a key enzyme in glutathione synthesis, and GSTs (glutathione S-transferases) via the ARE (antioxidant-response element). The Mrp2 (multidrug-resistance protein 2) pump mediates the excretion of GSH and GSSG excretion as well as endo- and xeno-biotics that are conjugated with GSH, glucuronate or sulphate. Considering that Mrp2 acts synergistically with these enzymes, we hypothesized that the regulation of Mrp2 gene expression is also dependent on Nrf2. Using BHA (butylated hydroxyanisole), which is a classical activator of the ARE–Nrf2 pathway, we observed an increase in the transcriptional activity of Mrp2, GCLC and Gsta1/Gsta2 genes in the mouse liver. A similar pattern of co-induction of Mrp2 and GCLC genes was also observed in mouse (Hepa 1-6) and human (HepG2) hepatoma cells treated with BHA, β-NF (β-naphthoflavone), 2,4,5-T (trichlorophenoxyacetic acid) or 2AAF (2-acetylaminofluorene), suggesting that these genes share common mechanism(s) of transcriptional activation in response to exposure to xenobiotics. To define the mechanism of Mrp2 gene induction, the 5′-flanking region of the mouse Mrp2 gene (2.0 kb) was isolated, and two ARE-like sequences were found: ARE-2 (−1391 to −1381) and ARE-1 (−95 to −85). Deletion analyses demonstrated that the proximal region (−185 to +99) contains the elements for the basal expression and xenobiotic-mediated induction of the Mrp2 gene. Gel-shift and supershift assays indicated that Nrf2–protein complexes bind ARE sequences of the Mrp2 promoter, preferentially to the ARE-1 sequence. Overexpression of Nrf2 increased ARE-1-mediated CAT (chloramphenicol acetyltransferase) gene activity, while overexpression of mutant Nrf2 protein repressed the activity. Thus Nrf2 appears to regulate Mrp2 gene expression via an ARE element located at the proximal region of its promoter in response to exposure to xenobiotics.
Characterization of Medicago truncatula (barrel medic) hydroperoxide lyase (CYP74C3), a water-soluble detergent-free cytochrome P450 monomer whose biological activity is defined by monomer–micelle association
Authors: Hughes Richard K. , Belfield Eric J. , Muthusamay Mylrajan , Khan Anuja , Rowe Arthur , Harding Stephen E. , Fairhurst Shirley A. , Bornemann Stephen , Ashton Ruth , Thorneley Roger N. F. , Casey Rod
Published: April 2006

We describe the detailed biochemical characterization of CYP74C3 (cytochrome P450 subfamily 74C3), a recombinant plant cytochrome P450 enzyme with HPL (hydroperoxide lyase) activity from Medicago truncatula (barrel medic). Steady-state kinetic parameters, substrate and product specificities, RZ (Reinheitszahl or purity index), molar absorption coefficient, haem content, and new ligands for an HPL are reported. We show on the basis of gel filtration, sedimentation velocity (sedimentation coefficient distribution) and sedimentation equilibrium (molecular mass) analyses that CYP74C3 has low enzyme activity as a detergent-free, water-soluble, monomer. The enzyme activity can be completely restored by re-activation with detergent micelles, but not detergent monomers. Corresponding changes in the spin state equilibrium, and probably co-ordination of the haem iron, are novel for cytochrome P450 enzymes and suggest that detergent micelles have a subtle effect on protein conformation, rather than substrate presentation, which is sufficient to improve substrate binding and catalytic-centre activity by an order of magnitude. The kcat/Km of up to 1.6×108 M−1·s−1 is among the highest recorded, which is remarkable for an enzyme whose reaction mechanism involves the scission of a C–C bond. We carried out both kinetic and biophysical studies to demonstrate that this effect is a result of the formation of a complex between a protein monomer and a single detergent micelle. Association with a detergent micelle rather than oligomeric state represents a new mechanism of activation for membrane-associated cytochrome P450 enzymes. Highly concentrated and monodispersed samples of detergent-free CYP74C3 protein may be well suited for the purposes of crystallization and structural resolution of the first plant cytochrome P450 enzyme.
Structure and stability of 2S albumin-type peanut allergens: implications for the severity of peanut allergic reactions
Authors: Lehmann Katrin , Schweimer Kristian , Reese Gerald , Randow Stefanie , Suhr Martin , Becker Wolf-Meinhard , Vieths Stefan , Rösch Paul
Published: April 2006

Resistance to proteolytic enzymes and heat is thought to be a prerequisite property of food allergens. Allergens from peanut (Arachis hypogaea) are the most frequent cause of fatal food allergic reactions. The allergenic 2S albumin Ara h 2 and the homologous minor allergen Ara h 6 were studied at the molecular level with regard to allergenic potency of native and protease-treated allergen. A high-resolution solution structure of the protease-resistant core of Ara h 6 was determined by NMR spectroscopy, and homology modelling was applied to generate an Ara h 2 structure. Ara h 2 appeared to be the more potent allergen, even though the two peanut allergens share substantial cross-reactivity. Both allergens contain cores that are highly resistant to proteolytic digestion and to temperatures of up to 100 °C. Even though IgE antibody-binding capacity was reduced by protease treatment, the mediator release from a functional equivalent of a mast cell or basophil, the humanized RBL (rat basophilic leukaemia) cell, demonstrated that this reduction in IgE antibody-binding capacity does not necessarily translate into reduced allergenic potency. Native Ara h 2 and Ara h 6 have virtually identical allergenic potency as compared with the allergens that were treated with digestive enzymes. The folds of the allergenic cores are virtually identical with each other and with the fold of the corresponding regions in the undigested proteins. The extreme immunological stability of the core structures of Ara h 2 and Ara h 6 provides an explanation for the persistence of the allergenic potency even after food processing.
Dual-function protein in plant defence: seed lectin from Dolichos biflorus (horse gram) exhibits lipoxygenase activity
Authors: Roopashree Subbaiah , Singh Sridevi Annapurna , Gowda Lalitha R. , Rao A. G. Appu
Published: April 2006

Plant–pathogen interactions play a vital role in developing resistance to pests. Dolichos biflorus (horse gram), a leguminous pulse crop of the subtropics, exhibits amazing defence against attack by pests/pathogens. Investigations to locate the possible source of the indomitable pest resistance of D. biflorus, which is the richest source of LOX (lipoxygenase) activity, have led to a molecule that exhibits LOX-like functions. The LOX-like activity associated with the molecule, identified by its structure and stability to be a tetrameric lectin, was found to be unusual. The evidence for the lectin protein with LOX activity has come from (i) MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS, (ii) N-terminal sequencing, (iii) partial sequencing of the tryptic fragments of the protein, (iv) amino acid composition, and (v) the presence of an Mn2+ ion. A hydrophobic binding site of the tetrameric lectin, along with the presence of an Mn2+ ion, accounts for the observed LOX like activity. This is the first ever report of a protein exhibiting both haemagglutination and LOX-like activity. The two activities are associated with separate loci on the same protein. LOX activity associated with this molecule adds a new dimension to our understanding of lectin functions. This observation has wide implications for the understanding of plant defence mechanisms against pests and the cellular complexity in plant–pathogen interactions that may lead to the design of transgenics with potential to impart pest resistance to other crops.
Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein
Authors: Nazarian Ramin , Starcevic Marta , Spencer Melissa J. , Dell'Angelica Esteban C.
Published: April 2006

Dysbindin was identified as a dystrobrevin-binding protein potentially involved in the pathogenesis of muscular dystrophy. Subsequently, genetic studies have implicated variants of the human dysbindin-encoding gene, DTNBP1, in the pathogeneses of Hermansky–Pudlak syndrome and schizophrenia. The protein is a stable component of a multisubunit complex termed BLOC-1 (biogenesis of lysosome-related organelles complex-1). In the present study, the significance of the dystrobrevin–dysbindin interaction for BLOC-1 function was examined. Yeast two-hybrid analyses, and binding assays using recombinant proteins, demonstrated direct interaction involving coiled-coil-forming regions in both dysbindin and the dystrobrevins. However, recombinant proteins bearing the coiled-coil-forming regions of the dystrobrevins failed to bind endogenous BLOC-1 from HeLa cells or mouse brain or muscle, under conditions in which they bound the Dp71 isoform of dystrophin. Immunoprecipitation of endogenous dysbindin from brain or muscle resulted in robust co-immunoprecipitation of the pallidin subunit of BLOC-1 but no specific co-immunoprecipitation of dystrobrevin isoforms. Within BLOC-1, dysbindin is engaged in interactions with three other subunits, named pallidin, snapin and muted. We herein provide evidence that the same 69-residue region of dysbindin that is sufficient for dystrobrevin binding in vitro also contains the binding sites for pallidin and snapin, and at least part of the muted-binding interface. Functional, histological and immunohistochemical analyses failed to detect any sign of muscle pathology in BLOC-1-deficient, homozygous pallid mice. Taken together, these results suggest that dysbindin assembled into BLOC-1 is not a physiological binding partner of the dystrobrevins, likely due to engagement of its dystrobrevin-binding region in interactions with other subunits.
Synergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria
Authors: Esteves Telma C. , Parker Nadeene , Brand Martin D.
Published: April 2006

The kinetics of proton transport through mammalian UCP1 (uncoupling protein 1) expressed in yeast mitochondria were measured. There was little or no UCP1 activity in the absence of added palmitate, but significant activity in its presence. The activator 4-HNE (4-hydroxy-2-nonenal) had little effect when added alone, but significantly enhanced proton conductance in the presence of added palmitate. Activation of the proton conductance of UCP1 was synergistic: proton conductance in the presence of both palmitate and 4-HNE was significantly greater than the sum of the individual effects. Mitochondria from control yeast transformed with empty vector showed no such synergy, showing that synergy is a property of UCP1. Activation by the 4-HNE analogue trans-cinnamate showed essentially the same characteristics as activation by 4-HNE. Mitochondria from brown adipose tissue also showed synergistic activation of GDP-sensitive proton conductance by palmitate and 4-HNE. These results show that reactive alkenals activate the proton conductance of UCP1 more strongly when fatty acids are also added, with implications for both mechanistic and physiological models of UCP1 activation.
The chemical chaperone CFcor-325 repairs folding defects in the transmembrane domains of CFTR-processing mutants
Authors: Loo Tip W. , Bartlett M. Claire , Wang Ying , Clarke David M.
Published: April 2006

Most patients with CF (cystic fibrosis) express a CFTR [CF TM (transmembrane) conductance regulator] processing mutant that is not trafficked to the cell surface because it is retained in the endoplasmic reticulum due to altered packing of the TM segments. CL4 (cytoplasmic loop 4) connecting TMs 10 and 11 is a ‘hot-spot’ for CFTR processing mutations. The chemical chaperone CFcor-325 (4-cyclohexyloxy-2-{1-[4-(4-methoxy-benezenesulphonyl)piperazin-1-yl]-ethyl}-quinazoline) rescued most CL4 mutants. To test if CFcor-325 promoted correct folding of the TMDs (TM domains), we selected two of the CL4 mutants (Q1071P and H1085R) for disulphide cross-linking analysis. Pairs of cysteine residues that were cross-linked in mature wild-type CFTR were introduced into mutants Q1071P and H1085R. The cross-linking patterns of the Q1071P or H1085R double cysteine mutants rescued with CFcor-325 were similar to those observed with mature wild-type double cysteine proteins. These results show that CFcor-325 rescued CFTR mutants by repairing the folding defects in the TMDs.
A quantitative lymphoscintigraphic evaluation of lymphatic function in the swollen hands of women with lymphoedema following breast cancer treatment
Authors: Stanton Anthony W. B. , Modi Stephanie , Mellor Russell H. , Peters A. Mike , Svensson William E. , Levick J. Rodney , Mortimer Peter S.
Published: April 2006

In BCRL (breast cancer-related lymphoedema), arm swelling is unevenly distributed and some regions are partly or entirely spared. In particular, the hand may or not be swollen, but when involved functional impairment can be substantial. We have found previously that, when the ipsilateral hand is spared of swelling (in a limb with swelling proximal to the hand), the local lymph drainage rate constant (k) is at least as high as in the contralateral hand, contrary to the traditional ‘stopcock’ concept of reduced lymph drainage from the whole limb. In the light of this finding, we have investigated lymph drainage in the hands of eight women with BCRL and moderate-to-severe hand swelling, using γ-camera quantitative lymphoscintigraphy. Images showed pronounced superficial activity in the ipsilateral swollen arms of most patients, indicating dermal backflow. k for 99mTc-labelled hIgG (human IgG) measured over 5 h in the subcutis of the ipsilateral swollen hand was 34±24% less than in the contralateral hand (P=0.013). Activity measured in the ipsilateral swollen forearm increased progressively, but there was very little increase in the contralateral forearm, indicating retention of 99mTc-labelled hIgG in the swollen forearm. It is concluded that lymphatic function in the swollen hand is impaired, and that there appears to be two populations of women with BCRL, i.e. spared-hand and swollen-hand, irrespective of the cancer treatment received.
The endogenous anti-angiogenic family of splice variants of VEGF, VEGFxxxb, are down-regulated in pre-eclamptic placentae at term
Authors: Bates David O. , MacMillan Philip P. , Manjaly Joseph G. , Qiu Yan , Hudson Sarah J. , Bevan Heather S. , Hunter Alyson J. , Soothill Peter W. , Read Michael , Donaldson Lucy F. , Harper Steven J.
Published: April 2006

PET (pre-eclamptic toxaemia) has recently been linked with alterations in production of a VEGFR1 [VEGF (vascular endothelial growth factor) receptor 1] splice variant that acts as a circulating inhibitor. We have recently described a family of naturally occurring splice variants of VEGF, termed VEGFxxxb, that also appear to act as inhibitors of conventional VEGFxxx-mediated angiogenesis. To determine whether alteration in splicing of VEGF–VEGFR family members extended beyond VEGFR1, we investigated the effect of pre-eclampsia on placental VEGFxxxb mRNA and protein expression. VEGFxxx and VEGFxxxb mRNA and protein were both found in normal human term placentae. VEGFxxx protein formed the majority of the total VEGF protein (980±195 pg/mg), whereas VEGFxxxb (11.5 pg/mg) was found to form a small part of the total VEGF protein expression (1.5±0.24%). Evidence for VEGF165b, VEGF121b and VEGF145b expression was found. In pre-eclamptic placentae, there was a significant down-regulation of VEGFxxxb isoforms, but a small up-regulation of VEGFxxx isoforms. In normal placenta VEGFxxxb and VEGFxxx concentrations were positively correlated (r=0.69, P<0.02), whereas in pre-eclamptic placentae, there was a significant negative correlation between VEGFxxxb and VEGFxxx protein expression (r=−0.8, P<0.02), indicating that there was a significant uncoupling of the splicing regulation of the VEGF isoforms. Combined with previous studies showing increased soluble VEGFR1 isoforms in human pre-eclampsia, these data suggest that there may be a common mechanism in pre-eclampsia that involves dysregulation of mRNA splicing of members of the VEGF–VEGFR axis.
Coherent control approaches to light guidance in the nanoscale
Authors: Sukharev Maxim , Seideman Tamar
Published: April 2006

Concepts of coherent control are extended to manipulate light in subdiffraction length scales via nanoparticle arrays. Phase and polarization control are first introduced and applied to control the pathway of electromagnetic energy through multiple branching nanoarray intersections, leading to an ultrafast optical nanoswitch below the diffraction limit. The genetic algorithm is next generalized to provide a systematic design tool, wherein both the properties of the excitation field and the structural parameters of the material system are optimized so as to make nanodevices with desired functionality. The scheme is used to gain insight into the interplay between the interactions that underlies the coherent propagation of electromagnetic energy via nanoparticle arrays. Implications to several research fields, including single molecule spectroscopy, spatially confined chemistry, optical logic, and nanoscale sensing, are envisioned.
Development of a novel instrument for microwave dielectric thermal analysis
Authors: Nair Biju Kumar S. , Parkes G. M. B. , Barnes P. A. , Sibley M. J. N. , Bond G.
Published: April 2006

The advantages of microwave heating in industrial processing are becoming more widely appreciated and the technique is of increasing commercial significance. However, knowledge of a material’s dielectric properties as a function of temperature is of considerable importance as they determine the efficiency with which the material converts microwave energy into heat. This article describes the development of a novel instrument for a new form of thermal analysis, microwave dielectric thermal analysis (MDTA) in which the sample is heated not conventionally but by microwaves, while its dielectric properties at microwave frequencies are determined quasisimultaneously using a network analyzer. A plot of the dielectric properties against temperature then gives the MDTA curve. The fundamental principle underlying the use of MDTA is that not only do a material’s dielectric properties (both the real and imaginary parts of the complex permittivity) alter (generally smoothly) as a function of temperature but dramatic differences can be found when chemical or physical changes occur. MDTA measures the sample’s dielectric properties as a function of temperature before, during, and after the chemical and/or physical changes occurring as it is heated in the microwave field and thus provides a unique way of studying them. Furthermore, due to the quasisimultaneous nature of the measurements, MDTA can also make a valuable contribution to the investigation of the so-called “microwave effect” anomalies that occur when certain materials are heated in a microwave field. We show that the technique can be used to study a wide range of thermal transformations, including solid-solid phase changes, melting, and chemical reactions, e.g., dehydration, via the complex permittivity-temperature profiles generated in MDTA.
On the extent of polymerization of liquid sulfur at very high temperatures
Authors: Andrikopoulos K. S. , Kalampounias A. G. , Yannopoulos S. N.
Published: April 2006

The extent of polymerization of liquid sulfur up to 731K has been obtained using Raman scattering. The data reveal the absence of a maximum in the polymerization curve. The obtained results are discussed in the spirit of computer simulations that suggest the existence of a maximum which depends on the bond breaking energy.
Photon echo spectroscopy of porphyrins and heme proteins: Effects of quasidegenerate electronic structure on the peak shift decay
Authors: Cho Byung Moon , Carlsson C. Fredrik , Jimenez Ralph
Published: April 2006

Three pulse photon echo peak shift spectroscopy and transient grating measurements on Zn-substituted cytochrome c, Zn-tetraphenylporphyrin, and Zn-protoporphyrin IX are reported. The effects of protein conformation, axial ligation, and solvent are investigated. Numerical simulations of the peak shift and transient grating experiments are presented. The simulations employed recently derived optical response functions for square-symmetric molecules with doubly degenerate excited states. Simulations exploring the effects of excited-state energy splitting, symmetric and asymmetric fluctuations, and excited-state lifetime show that the time scales of the peak shift decay in the three-level system largely reflect the same dynamics as in the two-level system. However, the asymptotic peak shift, which is a clear indicator of inhomogeneous broadening in a two-level system, must be interpreted more carefully for three-level systems, as it is also influenced by the magnitude of the excited-state splitting. The calculated signals qualitatively reproduce the data.
Analysis of uncertainties in polymer viscoelastic properties obtained from equilibrium computer simulations
Authors: Sen Suchira , Kumar Sanat K. , Keblinski Pawel
Published: April 2006

We critically evaluate the uncertainties in the stress autocorrelation function obtained from equilibrium molecular dynamics simulation of model polymer melts. This quantity is central to evaluating transport properties, e.g., the complex modulus and the viscosity. In contrast to the intuitive expectation that simulations have to be run five to six orders of magnitude longer than the chain relaxation time to reduce uncertainties to acceptable levels, our analysis shows that the majority of the uncertainty is associated with rapidly oscillating bonded interactions. These fluctuations occur on time scales which are approximately 104 times shorter than the relaxation time of a chain of length 80. Consequently, the effects of these oscillations on the stress autocorrelation function can be dramatically reduced by (i) conducting long simulations (typically 106 times longer than the bond relaxation times or only 102 chain relaxation times) and (ii) by performing running averages with time windows whose time scales are much longer than these oscillations. Conducting such long simulations also allows for the accurate determination of the melt viscosity and the low-frequency complex modulus, but performing running averages do not impact these quantities since they are time integrals of the stress autocorrelation function.
Rovibrational spectroscopy calculations of neon dimer using a phase space truncated Weyl-Heisenberg wavelet basis
Authors: Lombardini Richard , Poirier Bill
Published: April 2006

In a series of earlier articles [B. Poirier J. Theor. Comput. Chem. 2, 65 (2003); B. Poirier and A. Salam J. Chem. Phys. 121, 1690 (2004); B. Poirier and A. Salam J. Chem. Phys. 121, 1740 (2004)], a new method was introduced for performing exact quantum dynamics calculations in a manner that formally defeats exponential scaling with system dimensionality. The method combines an optimally localized, orthogonal Weyl-Heisenberg wavelet basis set with a simple phase space truncation scheme, and has already been applied to model systems up to 17degrees of freedom (DOF’s). In this paper, the approach is applied for the first time to a real molecular system (neon dimer), necessitating the development of an efficient numerical scheme for representing arbitrary potential energy functions in the wavelet representation. All bound rovibrational energy levels of neon dimer are computed, using both one DOF radial coordinate calculations and a three DOF Cartesian coordinate calculation. Even at such low dimensionalities, the approach is found to be competitive with another state-of-the-art method applied to the same system [J. Montgomery and B. Poirier J. Chem. Phys. 119, 6609 (2003)].
Generalized trajectory surface hopping method based on the Zhu-Nakamura theory
Authors: Oloyede Ponmile , Mil’nikov Gennady , Nakamura Hiroki
Published: April 2006

We present a generalized formulation of the trajectory surface hopping method applicable to a general multidimensional system. The method is based on the Zhu-Nakamura theory of a nonadiabatic transition and therefore includes the treatment of classically forbidden hops. The method uses a generalized recipe for the conservation of angular momentum after forbidden hops and an approximation for determining a nonadiabatic transition direction which is crucial when the coupling vector is unavailable. This method also eliminates the need for a rigorous location of the seam surface, thereby ensuring its applicability to a wide class of chemical systems. In a test calculation, we implement the method for the DH2+ system, and it shows a remarkable agreement with the previous results of C. Zhu, H. Kamisaka, and H. Nakamura, [J. Chem. Phys. 116, 3234 (2002)]. We then apply it to a diatomic-in-molecule model system with a conical intersection, and the results compare well with exact quantum calculations. The successful application to the conical intersection system confirms the possibility of directly extending the present method to an arbitrary potential of general topology.
Agarose-stabilized gold nanoparticles for surface-enhanced Raman spectroscopic detection of DNA nucleosides
Authors: Kattumuri V. , Chandrasekhar M. , Guha S. , Raghuraman K. , Katti K. V. , Ghosh K. , Patel R. J.
Published: April 2006

We present surface-enhanced Raman scattering (SERS) studies of DNA nucleosides using biologically benign agarose-stabilized gold nanoparticles (AAuNP). We compare the SERS activity of nucleosides with AAuNP to that of commercially obtained citrate-stabilized gold nanoparticles and find the SERS activity to be an order of magnitude higher with AAuNP. The higher SERS activity is explained in terms of the agarose matrix, which provides pathways for the gold nanoparticles to have distinct arrangements that result in stronger internal plasmon resonances.
Submersible digital in-line holographic microscope
Authors: Jericho S. K. , Garcia-Sucerquia J. , Xu Wenbo , Jericho M. H. , Kreuzer H. J.
Published: April 2006

Few instruments exist that can image microscopic marine organisms in their natural environment so that their locomotion mechanisms, feeding habits, and interactions with surfaces, such as biofouling, can be investigated in situ. We describe here the design and performance of a simple submersible digital in-line holographic microscope that can image organisms and their motion with micron resolution and that can be deployed from small vessels. Holograms and reconstructed images of several microscopic aquatic organisms were successfully obtained down to a depth of 20m. Important microscope characteristics such as the effect of camera pixel size on lateral and depth resolutions as well as the maximum sample volume that can be imaged with a given resolution are discussed in detail.
Estimating thermal diffusivity and specific heat from needle probe thermal conductivity data
Authors: Waite William F. , Gilbert Lauren Y. , Winters William J. , Mason David H.
Published: April 2006

Thermal diffusivity and specific heat can be estimated from thermal conductivity measurements made using a standard needle probe and a suitably high data acquisition rate. Thermal properties are calculated from the measured temperature change in a sample subjected to heating by a needle probe. Accurate thermal conductivity measurements are obtained from a linear fit to many tens or hundreds of temperature change data points. In contrast, thermal diffusivity calculations require a nonlinear fit to the measured temperature change occurring in the first few tenths of a second of the measurement, resulting in a lower accuracy than that obtained for thermal conductivity. Specific heat is calculated from the ratio of thermal conductivity to diffusivity, and thus can have an uncertainty no better than that of the diffusivity estimate. Our thermal conductivity measurements of ice Ih and of tetrahydrofuran (THF) hydrate, made using a 1.6mm outer diameter needle probe and a data acquisition rate of 18.2points∕s, agree with published results. Our thermal diffusivity and specific heat results reproduce published results within 25% for ice Ih and 3% for THF hydrate.
Cryogenic amplifier for intermediate source impedance with gigahertz bandwidth
Authors: Gustavsson S. , Gunnarsson D. , Delsing P.
Published: April 2006

We demonstrate a cryogenic amplifier for intermediate impedance sources, which operates from dc up to 1GHz. The amplifier is based on rf operation of many parallelly coupled single-electron transistors (SETs). Unlike the ordinary radio-frequency single-electron transistor this amplifier operates without a tank circuit, impedance matching is achieved by coupling many SETs in parallel. The input impedance is purely capacitive, with a very small capacitance of 16fF, and the frequency independent voltage noise is 10nV∕Hz.
Thickness-twist modes in a rectangular piezoelectric resonator of hexagonal crystals
Authors: Yang Jiashi , Guo Shaohua
Published: April 2006

Exact, simple expressions are obtained for thickness-twist vibration modes in a rectangular plate piezoelectric resonator of hexagonal crystals. The results are fundamental and useful to the understanding and design of piezoelectric resonators and acoustic wave sensors made of polarized ceramics, ZnO, and AlN.
Fluorine negative ion density measurement in a dual frequency capacitive plasma etch reactor by cavity ring-down spectroscopy
Authors: Booth Jean-Paul , Corr Cormac S. , Curley Garrett A. , Jolly Jacques , Guillon Jean , Földes Tomas
Published: April 2006

F − negative ions were detected by direct observation of the weak photodetachment absorption continuum below 364.5nm by cavity ring-down spectroscopy. The negative ions were generated in a modified industrial dielectric plasma etch reactor, with 2+27MHz dual frequency capacitive excitation in Ar∕CF4∕O2 and Ar∕C4F8∕O2 gas mixtures. The F− signal was superimposed on an unidentified absorption continuum, which was diminished by O2 addition. The F− densities were in the range of (0.5–3)×1011cm−3, and were not significantly different for single (27MHz) or dual (2+27MHz) frequency excitation, not confirming recent modeling predictions.
Detection of residual stresses in Pb(Zr0.53Ti0.47)O3 thin films prepared on LaNiO3 buffered metal substrates with Raman spectroscopy
Authors: Cheng Jinrong , He Liang , Yu Shengwen , Meng Zhongyan
Published: April 2006

Sol-gel derived Pb(Zr0.53Ti0.47)O3 (PZT) thin films have been prepared on LaNiO3 buffered Si, Ti, NiCr, and stainless steel. Raman scattering was carried out on both PZT thin films and powders. Compared with PZT powders, notable shifts of Raman modes to the lower frequency were observed in the spectra of PZT thin films on metal substrates, whereas to a higher frequency for PZT on Si. The correlation between Raman shifts and thermal stresses agrees well with the Curie-Weiss law, which indicates that the Raman scattering technique provides an effective way to estimate the magnitude and types of residual stresses in the film.
X-ray irradiation effects in top contact, pentacene based field effect transistors for space related applications
Authors: Devine R. A. B. , Ling Mang-Mang , Mallik Abhijit Basu , Roberts Mark , Bao Zhenan
Published: April 2006

Preliminary studies of the effect of x-ray irradiation, typically used to simulate radiation effects in space, on top contact, pentacene based field effect transistors have been carried out. Threshold voltage shifts in irradiated devices are consistent with positive charge trapping in the gate dielectric and a rebound effect is observed, independent of the sign of applied electric field during irradiation. Carrier mobility variations in positive electric field biased/irradiated devices are interpreted in terms of the effects of interface-state-like defects.