bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Palaeozoic intracratonic shears and post-tectonic cooling in the Rauer Group, Prydz Bay, East Antarctica constrained by40Ar/39Ar thermochronology
Authors: Wilson Christopher J.L. , Quinn Cameron , Tong Laixi , Phillips David
Published: June 2007

The Rauer Group, in Prydz Bay, contains reworked Archaean-Proterozoic crust in high-strain zones that formed during a pervasive high-temperature ductile deformation event related to intracratonic mechanisms. The effects of this event extend southwards from Prydz Bay into the southern Prince Charles Mountains. The associated structural evolution involved development of ductile and brittle structures that formed during an approximately north–south directed transpressional deformation event that is confined to high-grade (>800°C) shear zones in the Rauer Group. Minerals from the Rauer Group, yield40Ar/39Ar cooling ages ranging from 560 to 460 Ma. Thermal histories derived from hornblende, biotite and feldspar suggest that the onset of rapid cooling began sometime prior to 510 Ma with cooling rates ofc. 42 to 33°C myr-1fromc. 510 Ma toc. 500 Ma. Whereas,40Ar/39Ar data obtained from plagioclase and K–feldspar suggest a slower cooling fromc. 500 Ma toc. 460 Ma with cooling rates from 5 to 2°C myr-1. These results demonstrate that the early Palaeozoic cooling history and comparable palaeostress regimes are regionally extensive, which has important implications for the tectonothermal and stress-field variability across Gondwana. The elevated thermal conditions would induce lithospheric weakening and promote the early Palaeozoic intraplate orogeny observed in eastern Antarctica with the development of a large intracratonic shear system.
Impact of 10 January 1997 geomagnetic storm on the nighttime Weddell Sea Anomaly: A study utilizing data provided by the TOPEX/Poseidon mission and the Defense Meteorological Satellite Program, and simulations generated by the Coupled Thermosphere/Ionosphere Plasmasphere model
Authors: Horvath Ildiko
Published: June 2007

This study investigates the evolution of 10 January 1997 magnetic storm and the nighttime space weather change created by the impact of the interplanetary shock wave and associated events on the ionosphere. Its aims are to trace the storm's energy flow dissipation and transportation processes and to learn about the response of nighttime ionosphere to these interplanetary events, focusing on the reaction of the nighttime Weddell Sea Anomaly (WSA). To track down the consequential space weather changes, multi‐instrument measurements and Coupled Thermosphere/Ionosphere Plasmasphere (CTIP) simulations were combined. As results show, the first response of nighttime WSA to the energy input in the magnetosphere, when BZ turned southward, was its ∼50% total electron content (TEC) and Ni increase maintained during the main phase, indicating long‐duration positive storm effects. At ∼0800 universal time (UT) the second such BZ event triggered the depletion of equatorial and northern midlatitude ionosphere, a signature of strong downward E × B plasma drift, and launched gravity waves. Following a period of very bright aurora, at ∼1200 UT, some southern midlatitude and subauroral plasma enhancements developed. TOPEX detected an enhancement between 45–65°S (dip), where the equatorward winds were most effective, with a sudden TEC drop‐off, a signature of the plasmapause. Particularly strong negative storm effects depleted the nighttime WSA's TEC‐Ni (∼45–50%) and O/N2 ratio (∼21%). The Bent model could simulate the WSA, but not the storm‐related ionospheric responses. CTIP simulations indicated equatorward winds causing downwellings and changes in the neutral atmospheric composition revealed by the O/N2 ratio. Joule heating and electric fields were the major geophysical factors observed changing space weather during this storm.
Field observations of wave‐driven water‐level gradients across a coral reef flat
Authors: Jago O. K. , Kench P. S. , Brander R. W.
Published: June 2007

Field measurements of still water surface elevations were obtained across a narrow leeward reef flat on Lady Elliot Island, Great Barrier Reef, Australia in June 2003. Stilling wells were deployed from the reef crest landward to the island beach, and waves and mean water levels were monitored over both rising and falling tides during low to moderate wave energy conditions. Wave setup of up to 13.8 cm above still water level occurred in the presence of incident waves of 0.4 m yielding maximum water surface slopes greater than 6°. Results show that the magnitude of wave setup varies both temporally and spatially across the reef with changing water depth. Setup is dominant on the reef edge at low tide, evolving into a dual setup system at both the reef edge and shoreline at midtide and finally a dominant shoreline setup at high tide. On Lady Elliot Island the dual setup system is considered to result from spatial differences in transformation and breaking of swell and wind waves at midtide stages. The presence of a dual setup system across a reef flat has not been previously identified in field or modeling studies and has potentially significant implications for reefal current development, sediment transport, and the stability of reef island shorelines.
Hydraulic/partitioning tracer tomography for characterization of dense nonaqueous phase liquid source zones
Authors: Yeh Tian‐Chyi J. , Zhu Junfeng
Published: June 2007

A new technology, hydraulic/partitioning tracer tomography (HPTT), is proposed to survey spatial distributions of hydraulic properties and dense nonaqueous phase liquids (DNAPLs) in the subsurface. HPTT is nothing more than a set of multiple hydraulic/partitioning tracer tests and synthesis of all the tests to map the spatial distributions. It involves injection of water at one borehole in a source zone to create a steady state forced gradient flow field, then release of conservative/partitioning tracers at the same borehole, and monitoring heads and tracer breakthroughs at the others. The same operation is repeated using different boreholes for the water and the tracer injections. To analyze the head and tracer data obtained from the proposed tomographic survey, a joint stochastic estimator was developed. Numerical experiments were then conducted to evaluate the effectiveness of HPTT as well as the stochastic estimator. Results show that prior knowledge of hydraulic heterogeneity is critical for mapping the distribution of DNAPLs. In addition, the results suggest that the proposed HPTT in conjunction with the stochastic estimator is potentially a viable tool for high‐resolution characterization of subsurface heterogeneity and contamination.
Structure and hydraulics of natural woody debris jams
Authors: Manners R. B. , Doyle M. W. , Small M. J.
Published: June 2007

Numerous studies exist on the hydraulics of woody debris jams and the mechanisms driving their geomorphic influence. While most hydraulic studies treat jams as single, solid objects, jams are clearly not individual cylindrical logs but rather an accumulation of pieces ranging in size from leaves and twigs to entire trunks. Here we treat debris jams as complex and porous accumulations of heterogeneous material to understand the relative importance of the different size fractions comprising a jam. We systematically dismantled three deflector debris jams in four stages, removing a total of 17,783 individual wood pieces, to experimentally manipulate jam porosity. We measured the surrounding velocity, shear stress, and drag force (FD). The assumption of nonporosity can result in a 10−20% overestimation of FD. Back‐calculated values of the combined drag coefficient and frontal area term (CDAF)calc represented the drag characteristics of natural debris jams, whereas separating frontal area (AF(emp)) and drag coefficient (CD) contributions in natural jams is misleading. Values of (CDAF)calc for each jam at each stage of removal captured the effects of size and composition of the jam. Wood piece size in debris jams dictates the surface area to volume relationship. This association in turn determines the rate at which FD and (CDAF)calc change with the addition of material. Only low‐porosity jams produce the geomorphic and hydraulic characteristics commonly associated with deflector jams. Our results on natural debris jams also illustrate the importance of employing variable wood size fractions when using woody debris jams for river restoration.
A geostatistical approach for quantification of contaminant mass discharge uncertainty using multilevel sampler measurements
Authors: Li K. Betty , Goovaerts Pierre , Abriola Linda M.
Published: June 2007

Contaminant mass discharge across a control plane downstream of a dense nonaqueous phase liquid (DNAPL) source zone has great potential to serve as a metric for the assessment of the effectiveness of source zone treatment technologies and for the development of risk‐based source‐plume remediation strategies. However, too often the uncertainty of mass discharge estimated in the field is not accounted for in the analysis. In this paper, a geostatistical approach is proposed to estimate mass discharge and to quantify its associated uncertainty using multilevel transect measurements of contaminant concentration (C) and hydraulic conductivity (K). The approach adapts thep‐field simulation algorithm to propagate and upscale the uncertainty of mass discharge from the local uncertainty models ofCandK. Application of this methodology to numerically simulated transects shows that, with a regular sampling pattern, geostatistics can provide an accurate model of uncertainty for the transects that are associated with low levels of source mass removal (i.e., transects that have a large percentage of contaminated area). For high levels of mass removal (i.e., transects with a few hot spots and large areas of near‐zero concentration), a total sampling area equivalent to 6∼7% of the transect is required to achieve accurate uncertainty modeling. A comparison of the results for different measurement supports indicates that samples taken with longer screen lengths may lead to less accurate models of mass discharge uncertainty. The quantification of mass discharge uncertainty, in the form of a probability distribution, will facilitate risk assessment associated with various remediation strategies.
Robustness of climate change signals in near term predictions up to the year 2030: Changes in the frequency of temperature extremes
Authors: Shiogama Hideo , Nozawa Toru , Emori Seita
Published: June 2007

This is the first study to examine whether human contributions to changes in extreme temperature indices have larger amplitudes than natural variability in near future (up to 2030) climate prediction. We performed 10 runs of the initial condition perturbed ensemble of a coupled atmosphere‐ocean general circulation model. In the near future, over most land areas, all 10 runs predict more frequent occurrences of warm nights and warm days, and less frequent cold nights and cold days, suggesting that human influences have become larger than natural variability. The fraction of areas where all runs agree on the direction of changes over land is less sensitive to ensemble sizes (for warm nights, 96% and 93% for 4 runs and 10 runs, respectively). The changes in the frequency of warm and cold extremes are mainly due to shifts in seasonal mean temperatures. Additionally snow cover affects the frequency of cold extremes in some areas.
Channel network scaling laws in submarine basins
Authors: Straub Kyle M. , Jerolmack Douglas J. , Mohrig David , Rothman Daniel H.
Published: June 2007

Fluvial drainage basin area is often related to channel length and local slope through power law relationships and the relatively small range of exponents observed in these relationships is thought to result from physical mechanisms. Proposed mechanisms assume that the observed correlation between drainage area and fluid discharge is caused by precipitation. Using high resolution DEMs of channelized continental slope settings offshore Monterey, CA and Brunei Darussalam we extracted submarine channel profiles and drainage area statistics from five basins. In‐situ and remote observations suggest discharge in these oceanic settings is determined by boundary conditions at the shelf‐edge. In spite of substantial differences in environment and physical process, the data yield submarine scaling exponents within the range of terrestrial (fluvial) observations. The convergence in scaling relationships from two very different settings supports theoretical arguments that channel network structure results from the aggregation of random walks.
Structure and ligand-binding site characteristics of the human P2Y11 nucleotide receptor deduced from computational modelling and mutational analysis
Authors: Zylberg Jacques , Ecke Denise , Fischer Bilha , Reiser Georg
Published: June 2007

The P2Y11-R (P2Y11 receptor) is a less explored drug target. We computed an hP2Y11-R (human P2Y11) homology model with two templates, bovine-rhodopsin (2.6 Å resolution; 1 Å=0.1 nm) and a hP2Y1–ATP complex model. The hP2Y11-R model was refined using molecular dynamics calculations and validated by virtual screening methods, with an enrichment factor of 5. Furthermore, mutational analyses of Arg106, Glu186, Arg268, Arg307 and Ala313 confirmed the adequacy of our hP2Y11-R model and the computed ligand recognition mode. The E186A and R268A mutants reduced the potency of ATP by one and three orders of magnitude respectively. The R106A and R307A mutants were functionally inactive. We propose that residues Arg106, Arg268, Arg307 and Glu186 are involved in ionic interactions with the phosphate moiety of ATP. Arg307 is possibly also H-bonded to N6 of ATP via the backbone carbonyl. Activity of ATP at the F109I mutant revealed that the proposed π-stacking of Phe109 with the adenine ring is a minor interaction. The mutation A313N, which is part of a hydrophobic pocket in the vicinity of the ATP C-2 position, partially explains the high activity of 2-MeS-ATP at P2Y1-R as compared with the negligible activity at the P2Y11-R. Inactivity of ATP at the Y261A mutant implies that Tyr261 acts as a molecular switch, as in other G-protein-coupled receptors. Moreover, analysis of cAMP responses seen with the mutants showed that the efficacy of coupling of the P2Y11-R with Gs is more variable than coupling with Gq. Our model also indicates that Ser206 forms an H-bond with Pγ (the γ-phosphate of the triphosphate chain of ATP) and Met310 interacts with the adenine moiety.
Snake-venom-derived Factor IX-binding protein specifically blocks the γ-carboxyglutamic acid-rich-domain-mediated membrane binding of human Factors IX and X
Authors: Gopinath Subash C. B. , Shikamoto Yasuo , Mizuno Hiroshi , Kumar Penmetcha K. R.
Published: June 2007

A potent anticoagulant protein, IX-bp (Factor IX binding protein), has been isolated from the venom of Trimeresurus flavoviridis (habu snake) and is known to bind specifically to the Gla (γ-carboxyglutamic acid-rich) domain of Factor IX. To evaluate the molecular basis for its anticoagulation activity, we assessed its interactions with various clotting factors. We found that the anticoagulation activity is primarily due to binding to the Gla domains of Factors IX and X, thus preventing these factors from recognizing phosphatidylserine on the plasma membrane. The present study suggests that ligands that bind to the Gla domains of Factors IX and X may have the potential to become novel anticoagulants.
Activation of NADPH oxidase by transforming growth factor-β in hepatocytes mediates up-regulation of epidermal growth factor receptor ligands through a nuclear factor-κB-dependent mechanism
Authors: Murillo Miguel M. , Carmona-Cuenca Irene , del Castillo Gaelle , Ortiz Conrad , Roncero César , Sánchez Aránzazu , Fernández Margarita , Fabregat Isabel
Published: June 2007

The TGF-β (transforming growth factor-β) induces survival signals in foetal rat hepatocytes through transactivation of EGFR (epidermal growth factor receptor). The molecular mechanism is not completely understood, but both activation of the TACE (tumour necrosis factor α-converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17; one of the metalloproteases involved in shedding of the EGFR ligands) and up-regulation of TGF-α and HB-EGF (heparin-binding epidermal growth factor-like growth factor) appear to be involved. In the present study, we have analysed the molecular mechanisms that mediate up-regulation of the EGFR ligands by TGF-β in foetal rat hepatocytes. The potential involvement of ROS (reactive oxygen species), an early signal induced by TGF-β, and the existence of an amplification loop triggered by initial activation of the EGFR, have been studied. Results indicate that DPI (diphenyleneiodonium) and apocynin, two NOX (NADPH oxidase) inhibitors, and SB431542, an inhibitor of the TβR-I (TGF-β receptor I), block up-regulation of EGFR ligands and Akt activation. Different members of the NOX family of genes are expressed in hepatocytes, included nox1, nox2 and nox4. TGF-β up-regulates nox4 and increases the levels of Rac1 protein, a known regulator of both Nox1 and Nox2, in a TβR-I-dependent manner. TGF-β mediates activation of the nuclear factor-κB pathway, which is inhibited by DPI and is required for up-regulation of TGF-α and HB-EGF. In contrast, EGFR activation is not required for TGF-β-induced up-regulation of those ligands. Considering previous work that has established the role of ROS in apoptosis induced by TGF-β in hepatocytes, the results of the present study indicate that ROS might mediate both pro- and anti-apoptotic signals in TGF-β-treated cells.
Enzymatic cleavage specificity of the proα1(V) chain processing analysed by site-directed mutagenesis
Authors: Bonod-Bidaud Christelle , Beraud Mickaël , Vaganay Elisabeth , Delacoux Frédéric , Font Bernard , Hulmes David J. S. , Ruggiero Florence
Published: June 2007

The proteolytic processing of procollagen V is complex and depends on the activity of several enzymes among which the BMP-1 (bone morphogenetic protein-1)/tolloid metalloproteinase and the furin-like proprotein convertases. Few of these processing interactions could have been predicted by analysing the presence of conserved consensus sequences in the proα1(V) chain. In the present study we opted for a cell approach that allows a straightforward identification of processing interactions. A construct encompassing the complete N-terminal end of the proα1(V) chain, referred to as Nα1, was recombinantly expressed to be used for enzymatic assays and for antibody production. Structural analysis showed that Nα1 is a monomer composed of a compact globule and an extended tail, which correspond respectively to the non-collagenous Nα1 subdomains, TSPN-1 (thrombospondin-1 N-terminal domain-like) and the variable region. Nα1 was efficiently cleaved by BMP-1 indicating that the triple helix is not required for enzyme activity. By mutating residues flanking the cleavage site, we showed that the aspartate residue at position P2′ is essential for BMP-1 activity. BMP-1 activity at the C-terminal end of the procollagen V was assessed by generating a furin double mutant (R1584A/R1585A). We showed that, in absence of furin activity, BMP-1 is capable of processing the C-propeptide even though less efficiently than furin. Altogether, our results provide new relevant information on this complex and poorly understood mechanism of enzymatic processing in procollagen V function.
A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane
Authors: Dufe Veronica T. , Ingner Daniel , Heby Olle , Khomutov Alex R. , Persson Lo , Al-Karadaghi Salam
Published: June 2007

The critical role of polyamines in key processes such as cell growth, differentiation and macromolecular synthesis makes the enzymes involved in their synthesis potential targets in the treatment of certain types of cancer and parasitic diseases. Here we present a study on the inhibition of human and Leishmania donovani ODC (ornithine decarboxylase), the first committed enzyme in the polyamine biosynthesis pathway, by APA (1-amino-oxy-3-aminopropane). The present study shows APA to be a potent inhibitor of both human and L. donovani ODC with a Ki value of around 1.0 nM. We also show that L. donovani ODC binds the substrate, the co-enzyme pyridoxal 5′-phosphate and the irreversible inhibitor α-difluoromethylornithine (a curative agent of West African sleeping sickness) with less affinity than human ODC. We have also determined the three-dimensional structure of human ODC in complex with APA, which revealed the mode of the inhibitor binding to the enzyme. In contrast with earlier reports, the structure showed no indication of oxime formation between APA and PLP (pyridoxal 5′-phosphate). Homology modelling suggests a similar mode of binding of APA to L. donovani ODC. A comparison of the ODC–APA–PLP structure with earlier ODC structures also shows that the protease-sensitive loop (residues 158–168) undergoes a large conformational change and covers the active site of the protein. The understanding of the structural mode of APA binding may constitute the basis for the development of more specific inhibitors of L. donovani ODC.
Transcriptional regulation of the distal promoter of the rat pyruvate carboxylase gene by hepatocyte nuclear factor 3β/Foxa2 and upstream stimulatory factors in insulinoma cells
Authors: Boonsaen Thirajit , Rojvirat Pinnara , Surinya Kathy H. , Wallace John C. , Jitrapakdee Sarawut
Published: June 2007

PC (pyruvate carboxylase) plays a crucial role in intermediary metabolism including glucose-induced insulin secretion in pancreatic islets. In the present study, we identified two regions of the 1.2 kb distal promoter, the −803/−795 site and the −408/−403 E-box upstream of the transcription start site, as the important cis-acting elements for transcriptional activation of the luciferase reporter gene. Site-directed mutagenesis of either one of these sites in the context of this 1.2 kb promoter fragment, followed by transient transfections in the insulinoma cell line, INS-1, abolished reporter activity by approx. 50%. However, disruption of either the −803/−795 or the −408/−403 site did not affect reporter gene activity in NIH 3T3 cells, suggesting that this promoter fragment is subjected to cell-specific regulation. The nuclear proteins that bound to these −803/−795 and −408/−403 sites were identified by gel retardation assays as HNF3β (hepatocyte nuclear factor 3β)/Foxa2 (forkhead/winged helix transcription factor box2) and USFs (upstream stimulatory factors), USF1 and USF2, respectively. Chromatin immunoprecipitation assays using antisera against HNF3β/Foxa2, USF1 and USF2 demonstrated that endogenous HNF3β/Foxa2 binds to the −803/−795 Foxa2 site, and USF1 and USF2 bind to the −408/−403 E-box respectively in vivo, consistent with the gel retardation assay results. Although there are weak binding sites located at regions −904 and −572 for PDX1 (pancreatic duodenal homeobox-1), a transcription factor that controls expression of β-cell-specific genes, it did not appear to regulate PC expression in INS-1 cells in the context of the 1.2 kb promoter fragment. The results presented here show that Foxa2 and USFs regulate the distal promoter of the rat PC gene in a cell-specific manner.
The Modulation of Haptic Line Bisection by a Visual Illusion and Optokinetic Stimulation
Authors: Gallace Alberto , Auvray Malika , Spence Charles
Published: June 2007

Research has shown that a variety of different sensory manipulations, including visual illusions, transcutaneous nerve stimulation, vestibular caloric stimulation, optokinetic stimulation, and prism adaptation, can all influence people's performance on spatial tasks such as line bisection. It has been suggested that these manipulations may act upon the ‘higher-order’ levels of representation used to code spatial information. We investigated whether we could influence haptic line bisection in normal participants crossmodally by varying the visual background that participants viewed. In experiment 1, participants haptically bisected wooden rods while looking at a variant of the Oppel–Kundt visual illusion. Haptic-bisection judgments were influenced by the orientation of the visual illusion (in line with previous unimodal visual findings). In experiment 2, haptic-bisection judgments were also influenced by the presence of a leftward or rightward moving visual background. In experiments 3 and 4, the position of the to-be-bisected stimuli was varied with respect to the participant's body midline. The results confirmed an effect of optokinetic stimulation, but not of the Oppel–Kundt illusion, on participants' tactile-bisection errors, suggesting that the two manipulations might differentially affect haptic processing. Taken together, these results suggest that the ‘higher-order’ levels of spatial representation upon which perceptual judgments and/or motor responses are made may have multisensory or amodal characteristics.
Differences in Attentional Involvement Underlying the Perception of Distinctive and Typical Faces
Authors: Ryu Jae-Jin , Chaudhuri Avi
Published: June 2007

Differences in human faces can be evaluated along a continuum that ranges from ‘distinctive’ to ‘typical.’ We examined processing differences between distinctive and typical faces by two attentional tasks that induce attentional blink (AB). Given that AB is believed to reflect temporal or capacity limits of attention, stimuli that survive AB are believed to be associated with greater processing efficiency. In a change-detection task, participants were required to detect changes in the two pairs of faces that were presented in rapid succession. Changes involving the distinctive face of a pair were more likely to be detected than those involving a typical face. In a face-identification task, distinctive faces embedded in a rapid serial visual presentation (RSVP) stream were identified with a greater accuracy than typical faces. Together, our results suggest that distinctive faces are associated with greater processing efficiency and may be explained in terms of perceptual salience, a stimulus dimension known to attract attention.
Accuracy of Head Orientation Perception in Triadic Situations: Experiment in a Virtual Environment
Authors: Poppe Ronald , Rienks Rutger , Heylen Dirk
Published: June 2007

Research has revealed high accuracy in the perception of gaze in dyadic (sender–receiver) situations. Triadic situations differ from these in that an observer has to report where a sender is looking, not relative to himself. This is more difficult owing to the less favourable position of the observer. The effect of the position of the observer on the accuracy of the identification of the sender's looking direction is relatively unexplored. Here, we investigate this, focusing exclusively on head orientation. We used a virtual environment to ensure good stimulus control. We found a mean angular error close to 5°. A higher observer viewpoint results in more accurate identification. Similarly, a viewpoint with a smaller angle to the sender's midsagittal plane leads to an improvement in identification performance. Also, we found an effect of underestimation of the error in horizontal direction, similar to findings for dyadic situations.
The role of NH+4 toxicity in the decline of the submersed macrophyte Vallisneria natans in lakes of the Yangtze River basin, China
Authors: Cao Te , Xie Ping , Ni Leyi , Wu Aiping , Zhang Min , Wu Shikai , Smolders A.J.P.
Published: June 2007

Experimental and field studies were conducted to evaluate the effects of NH4+ enrichment on growth and distribution of the submersed macrophyte, Vallisneria natans L, in lakes of the Yangtze River in China, based on the balance between free amino acids (FAA) and soluble carbohydrates (SC) in the plant tissue. Increase of NH4+ rather than NO3– concentrations in the water column caused FAA accumulation and SC depletion of the plant. The plant showed a unimodal pattern of biomass distribution along both FAA/SC ratios and external NH4+ concentrations, indicating that a moderate NH4-N concentration (<0.3 mg L–1) benefited the plant, whereas the high NH4-N concentration (>0.56 mg L–1) eliminated the plant completely. Therefore, 0.56 mg NH4-N mg L–1 in the water column was taken as the upper limit for V. natans in lakes of the Yangtze River basin. The mesocosm experiment showed that at a high external NH4-N (0.81 mg L–1), V. natans failed to propagate with a loss of half SC content (5 mg g–1 DW) in the rhizomes, indicating that the consumption of carbohydrates for detoxification of excess NH4+ into non-toxic FAA significantly diminished carbohydrate supply to the rhizomes. This might consequently inhibit the vegetative reproduction of the plant, and also might be an important cause for the decline and disappearance of the plant with eutrophication. The present study for the first time reports substantial ecophysiological evidences for NH4+ stress to submersed macrophytes, and indicates that NH4+ toxicity arising from eutrophication probably plays a key role in the deterioration of submersed macrophytes like V. natans.
Prediction of Ras-effector interactions using position energy matrices
Authors: Kiel Christina , Serrano Luis
Published: June 2007

Motivation: One of the more challenging problems in biology is to determine the cellular protein interaction network. Progress has been made to predict protein–protein interactions based on structural information, assuming that structural similar proteins interact in a similar way. In a previous publication, we have determined a genome-wide Ras-effector interaction network based on homology models, with a high accuracy of predicting binding and non-binding domains. However, for a prediction on a genome-wide scale, homology modelling is a time-consuming process. Therefore, we here successfully developed a faster method using position energy matrices, where based on different Ras-effector X-ray template structures, all amino acids in the effector binding domain are sequentially mutated to all other amino acid residues and the effect on binding energy is calculated. Those pre-calculated matrices can then be used to score for binding any Ras or effector sequences.

Results: Based on position energy matrices, the sequences of putative Ras-binding domains can be scanned quickly to calculate an energy sum value. By calibrating energy sum values using quantitative experimental binding data, thresholds can be defined and thus non-binding domains can be excluded quickly. Sequences which have energy sum values above this threshold are considered to be potential binding domains, and could be further analysed using homology modelling. This prediction method could be applied to other protein families sharing conserved interaction types, in order to determine in a fast way large scale cellular protein interaction networks. Thus, it could have an important impact on future in silico structural genomics approaches, in particular with regard to increasing structural proteomics efforts, aiming to determine all possible domain folds and interaction types.

Availability: All matrices are deposited in the ADAN database (http://adan-embl.ibmc.umh.es/).

Contact:  christina.kiel@crg.es

Supplementary information: Supplementary data are available at Bioinformatics online.
Improving gene quantification by adjustable spot-image restoration
Authors: Daskalakis Antonis , Cavouras Dionisis , Bougioukos Panagiotis , Kostopoulos Spiros , Glotsos Dimitris , Kalatzis Ioannis , Kagadis George C. , Argyropoulos Christos , Nikiforidis George
Published: June 2007

Motivation: One of the major factors that complicate the task of microarray image analysis is that microarray images are distorted by various types of noise. In this study a robust framework is proposed, designed to take into account the effect of noise in microarray images in order to assist the demanding task of microarray image analysis. The proposed framework, incorporates in the microarray image processing pipeline a novel combination of spot adjustable image analysis and processing techniques and consists of the following stages: (1) gridding for facilitating spot identification, (2) clustering (unsupervised discrimination between spot and background pixels) applied to spot image for automatic local noise assessment, (3) modeling of local image restoration process for spot image conditioning (adjustable wiener restoration using an empirically determined degradation function), (4) automatic spot segmentation employing seeded-region-growing, (5) intensity extraction and (6) assessment of the reproducibility (real data) and the validity (simulated data) of the extracted gene expression levels.

Results: Both simulated and real microarray images were employed in order to assess the performance of the proposed framework against well-established methods implemented in publicly available software packages (Scanalyze and SPOT). Regarding simulated images, the novel combination of techniques, introduced in the proposed framework, rendered the detection of spot areas and the extraction of spot intensities more accurate. Furthermore, on real images the proposed framework proved of better stability across replicates. Results indicate that the proposed framework improves spots’ segmentation and, consequently, quantification of gene expression levels.

Availability: All algorithms were implemented in Matlab™ (The Mathworks, Inc., Natick, MA, USA) environment. The codes that implement microarray gridding, adaptive spot restoration and segmentation/intensity extraction are available upon request. Supplementary results and the simulated microarray images used in this study are available for download from: ftp://users:bioinformatics@mipa.med.upatras.gr

Contact:  daskalakis@med.upatras.gr

Supplementary information: Supplementary data are available at Bioinformatics online.
Genomic mutation consequence calculator
Authors: Major John E.
Published: June 2007

Summary: The genomic mutation consequence calculator (GMCC) is a tool that will reliably and quickly calculate the consequence of arbitrary genomic mutations. GMCC also reports supporting annotations for the specified genomic region. The particular strength of the GMCC is it works in genomic space, not simply in spliced transcript space as some similar tools do. Within gene features, GMCC can report on the effects on splice site, UTR and coding regions in all isoforms affected by the mutation. A considerable number of genomic annotations are also reported, including: genomic conservation score, known SNPs, COSMIC mutations, disease associations and others. The manual interface also offers link outs to various external databases and resources. In batch mode, GMCC returns a csv file which can easily be parsed by the end user.

Audience: GMCC is intended to support the many tumor resequencing efforts, but can be useful to any study investigating genomic mutations.

Availability: GMCC is freely available via a web portal with a manual mode and a batch query mode. It may be found at this URL: http://cbio.mskcc.org/gmcc

Contact:  majorj@mskcc.org

Supplementary information: A FAQ and examples can be found at the URL above.
Identification of aberrant chromosomal regions from gene expression microarray studies applied to human breast cancer
Authors: Buness Andreas , Kuner Ruprecht , Ruschhaupt Markus , Poustka Annemarie , Sültmann Holger , Tresch Achim
Published: June 2007

Motivation: In cancer, chromosomal imbalances like amplifications and deletions, or changes in epigenetic mechanisms like DNA methylation influence the transcriptional activity. These alterations are often not limited to a single gene but affect several genes of the genomic region and may be relevant for the disease status. For example, the ERBB2 amplicon (17q21) in breast cancer is associated with poor patient prognosis. We present a general, unsupervised method for genome-wide gene expression data to systematically detect tumor patients with chromosomal regions of distinct transcriptional activity. The method aims to find expression patterns of adjacent genes with a consistently decreased or increased level of gene expression in tumor samples. Such patterns have been found to be associated with chromosomal aberrations and clinical parameters like tumor grading and thus can be useful for risk stratification or therapy.

Results: Our approach was applied to 12 independent human breast cancer microarray studies comprising 1422 tumor samples. We prioritized chromosomal regions and genes predominantly found across all studies. The result highlighted not only regions which are well known to be amplified like 17q21 and 11q13, but also others like 8q24 (distal to MYC) and 17q24-q25 which may harbor novel putative oncogenes. Since our approach can be applied to any microarray study it may become a valuable tool for the exploration of transcriptional changes in diverse disease types.

Availability: The R source codes which implement the method and an exemplary analysis are available at http://www.dkfz.de/mga2/people/buness/CTP/.

Contact:  a.buness@gmx.de

Supplementary information: Supplementary data are available at Bioinformatics online.
ChemDB update—full-text search and virtual chemical space
Authors: Chen Jonathan H. , Linstead Erik , Swamidass S. Joshua , Wang Dennis , Baldi Pierre
Published: June 2007

ChemDB is a chemical database containing nearly 5M commercially available small molecules, important for use as synthetic building blocks, probes in systems biology and as leads for the discovery of drugs and other useful compounds. The data is publicly available over the web for download and for targeted searches using a variety of powerful methods. The chemical data includes predicted or experimentally determined physicochemical properties, such as 3D structure, melting temperature and solubility. Recent developments include optimization of chemical structure (and substructure) retrieval algorithms, enabling full database searches in less than a second. A text-based search engine allows efficient searching of compounds based on over 65M annotations from over 150 vendors. When searching for chemicals by name, fuzzy text matching capabilities yield productive results even when the correct spelling of a chemical name is unknown, taking advantage of both systematic and common names. Finally, built in reaction models enable searches through virtual chemical space, consisting of hypothetical products readily synthesizable from the building blocks in ChemDB.

Availability: ChemDB and Supplementary Materials are available at http://cdb.ics.uci.edu.

Contact:  pfbaldi@ics.uci.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
QPRIMER: a quick web-based application for designing conserved PCR primers from multigenome alignments
Authors: Kim Namshin , Lee Christopher
Published: June 2007

Summary: We have developed a quick web-based application for designing conserved genomic PCR and RT-PCR primers from multigenome alignments targeting specific exons or introns. We used Pygr (The Python Graph Database Framework for Bioinformatics) to query intervals from multigenome alignments, which gives us less than a millisecond access to any intervals of any genome within multigenome alignments. PRIMER3 was used to extract optimal primers from a gene of interest. QPRIMER creates an electronic genomic PCR image from a set of conserved primers as well as summary pages for primer alignments and products. QPRIMER supports human, mouse, rat, chicken, dog, zebrafish and fruit fly.

Availability:  http://www.bioinformatics.ucla.edu/QPRIMER/

Contact:  leec@mbi.ucla.edu
Comparative Transcriptome Analysis Reveals Common and Specific Tags for Root Hair and Crack-Entry Invasion inSesbania rostrata
Authors: Capoen Ward , Den Herder Jeroen , Rombauts Stephane , De Gussem Jeroen , De Keyser Annick , Holsters Marcelle , Goormachtig Sofie
Published: June 2007

The tropical legume Sesbania rostrata provides its microsymbiont Azorhizobium caulinodans with versatile invasion strategies to allow nodule formation in temporarily flooded habitats. In aerated soils, the bacteria enter via the root hair curling mechanism. Submergence prevents this epidermal invasion by accumulation of inhibiting concentrations of ethylene and, under these conditions, the bacterial colonization occurs via intercellular cortical infection at lateral root bases. The transcriptome of both invasion ways was compared by cDNA-amplified fragment length polymorphism analysis. Clusters of gene tags were identified that were specific for either epidermal or cortical invasion or were shared by both. The data provide insight into mechanisms that control infection and illustrate that entry via the epidermis adds a layer of complexity to rhizobial invasion.
Discovery of antibacterial cyclic peptides that inhibit the ClpXP protease
Authors: Cheng Lin , Naumann Todd A. , Horswill Alexander R. , Hong Sue‐Jean , Venters Bryan J. , Tomsho John W. , Benkovic Stephen J. , Keiler Kenneth C.
Published: June 2007

A method to rapidly screen libraries of cyclic peptides in vivo for molecules with biological activity has been developed and used to isolate cyclic peptide inhibitors of the ClpXP protease. Fluorescence activated cell sorting was used in conjunction with a fluorescent reporter to isolate cyclic peptides that inhibit the proteolysis of tmRNA‐tagged proteins in Escherichia coli. Inhibitors shared little sequence similarity and interfered with unexpected steps in the ClpXP mechanism in vitro. One cyclic peptide, IXP1, inhibited the degradation of unrelated ClpXP substrates and has bactericidal activity when added to growing cultures of Caulobacter crescentus, a model organism that requires ClpXP activity for viability. The screen used here could be adapted to identify cyclic peptide inhibitors of any enzyme that can be expressed in E. coli in conjunction with a fluorescent reporter.
In vivo recovery and early half‐life of infused factor VIII in haemophilia A
Authors: Kasper Carol K.
Published: June 2007

Between 1980 and 1994, 169 in vivo recovery studies were performed in one haemophilia centre on casually‐recruited outpatients with severe haemophilia A, and 149 early‐phase half‐life studies were performed on patients scheduled for elective surgery. Average recoveries improved from 80% to 97% of the expected values over the study period. No relationship of recovery to level of product purification was seen. In the disappearance studies, plasma factor VIII levels fell to half the peak levels by 3.25h after infusion, on average.
Immune tolerance therapy in paediatric haemophiliacs with factor VIII inhibitors: 14 years follow‐up
Authors: Kreuz W. , Ehrenforth S. , Funk M. , Auerswald G. , Mentzer D. , Joseph‐Steiner J. , Beeg T. , Klarman D. , Scharrer I. , Kornhuber B.
Published: June 2007

We report our clinical experience in the immune tolerance (IT) therapy of 21 paediatric haemophiliacs with FVIII inhibitor: high responders (16HR) received initially FVIII twice daily at a dosage of 50–300 U/kg/day, 11/16 received a concomitant treatment with activated prothrombin complex concentrate (100–200 U/kg/day). Low responders (five LR) received 20–100 FVIII U/kg every second or third day. Inhibitor elimination was achieved in 19/21 patients in a median time of 4 months in HR and 1.5 months in LR. The outcome and length of time needed to induce IT was significantly correlated with FVIII exposure between the first inhibitor detection and onset of IT therapy and to interruption of IT therapy. For a rapid elimination of FVIII inhibitors it is important to start continuous administration of high‐dose FVIII (≥ 100 FVIII U/kg/day) before repeated exposure to FVIII, in order to prevent rebooster effects, prolongation of elimination time, and to reduce expense.
Effect and side‐effects of alpha interferon treatment in haemophilia patients with chronic hepatitis C
Authors: Mauser‐Bunschoten E. P. , Bresters D. , Reesink H. W. , Roosendaal G. , Chamuleau R. A. F. M. , Haan E. , Jansen P. L. M. , van den Berg H. M.
Published: June 2007

To evaluate the effect and side‐effects of alpha interferon 2B (IFN) treatment in haemophilia patients with chronic hepatitis C (positive HCV antibody test, positive HCV‐RNA test and ALT levels >2.5 × upper limit of normal) eight HIV and HBs‐ag negative haemophilia patients were treated with IFN for 26 weeks in a dosage of 5 mega units (MU) daily for 2 weeks, 2.5 MU daily for 4 weeks and 1.5 MU 3 times a week for 20 weeks. Patients who were transient or non‐responders after 26 weeks of IFN therapy were treated for 2.5 years with 5 MU IFN three times a week. At the end of 3 years follow‐up, four patients were considered complete responders (HCV‐RNA negative) with complete and sustained ALT normalization and disappearance from HCV‐RNA from blood, two patients only showed a transient response and two patients were non‐responders.

All patients experienced the common side‐effects of IFN treatment. Two patients complained about feelings of depression and impotence. For both this was the reason to stop IFN treatment. In one patient, IFN treatment was stopped 90 weeks after start of therapy because of persistent fatigue. In another patient the dosage was adjusted because of a decrease in platelet count.

No effect of IFN on bleeding frequency and chronic arthopathy was seen.

We conclude that the clinical effects and side‐effects of IFN therapy in patients with haemophilia and chronic hepatitis C are comparable with those of non‐haemophilia patients with chronic hepatitis C. Haemophilia patients can be treated for chronic hepatitis C infection in the same way as patients without haemophilia.
The feasibility of using concentrates containing factor IX for continuous infusion
Authors: SCHULMAN SAM , GITEL SANFORD , ZIVELIN ARIELA , KATSAROU OLGA , MANDALAKI TITIKA , VARON DAVID , MARTINOWITZ URI
Published: June 2007

We have investigated the feasibility of continuous infusion of undiluted factor IX (F IX) over several days using minipumps. The stabilities of seven different reconstituted F IX products were substantially better than those declared by the manufacturers. Several concentrates maintained factor activities 80% of baseline for the entire period of 4 weeks at 4‐8d̀C as did one product at 20–23d̀A. At 37d̀C the latter concentrate was stable for at least 1 week. The stability seemed to correlate with the purity of the product. Analysis of two prothrombin comples concentrates by gel electrophoresis demonstrated degradation of prothrombin to prethrombin‐1 and fragment 1 at 37d̀C and in one of the concentrates also at 20–23d̀C. In two F IX concentrates the corresponding analysis did not reveal any degradation. Four patients were treated with continuous infusion with a pure F IX concentrate (Mononine™, Armour) after surgery or for serious haemorrhage (two each) with good haemostatic effect, an initial progressive decrease of the F IX clearance, and no side‐effects. Continuous infusion with F IX, using a minipump and undiluted reconstituted factor, is therefore feasible and effective, and can be conveniently prepared for several days at a time. Pure F IX products are more stable and probably safer for this purpose.