bluuebunny/crossref_metadata_2025 huggingface dataset:
Reference ranges for fetal ventricular width: a non‐normal approach
Authors: Salomon L. J. , Bernard J. P. , Ville Y.
Published: May 2007

Objectives

Normal ranges for fetal cerebral ventricular width are usually based on parametric methods, which define cut‐off values based on means and standard deviations. We aimed to construct reference charts based on a large sample and using a method that better fits with skewed measurements.

Methods

In November 2001–December 2005, a single operator, who was unaware of the subsequent analysis, performed prospectively and routinely fetal cerebral ventricular width measurements. We used the LMS method (which summarizes the changing distribution of a variable of interest according to a covariate (gestational age) using three curves representing the median (M), the coefficient of variation (S) and skewness (L)) to describe the distribution of measurements with gestational age. The LMS method provides a general method for fitting smooth centile curves to reference data. It utilizes the power transformation family of Box and Cox to allow the skewness of the measurement distribution, as well as the median and variability, to vary with age. The theoretical proportion of fetal ventricular widths ≥ 10 mm based on the LMS method and on methods based on the assumption of normality were compared with the actual proportion using binomial tests. The influence on ventricular size of gestational age and fetal gender and presentation was assessed using robust regression methods.

Results

Included in the study were 4769 ventricular measurements, 42 (0.88%) of which were ≥ 10 mm. The LMS method allowed us to fit the skewness of the measurements and identified slight changes throughout gestation. The actual proportion of measurements ≥ 10 mm was not different from that expected according to the LMS method (0.88% vs. 1%, P = 0.25), whereas it was significantly different from that based on the classical normal approximation (0.88% vs. 0.4%, P < 0.0001). There was a significant difference with gender (males: + 0.29 ± 0.042 mm as compared to females, P < 0.0001), but there was no difference with fetal presentation (P = 0.4).

Conclusion

We present new reference values for fetal ventricular width based on the LMS method. A fixed cut‐off value of 10 mm identifies around 1% of the population throughout gestation, which is more than that calculated in previous studies. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.
Theory of Vibration of Buildings During Earthquake
Authors: Biot M.
Published: May 2007

Die Bewegungen eines Gebäudes, das von einem Erdbeben getroffen wird, haben den Charakter Vorübergehender Schwingungen. Die Untersuchung derartiger Vorgänge nach dem Heaviside‐Verfahren ist den Elektro‐Ingenieuren geläufig. Für den Fall der Erdbewegung zu mühsam. Außerdem braucht man nicht die Bewegung eines Gebäudes genau zu kennen, sondern nur die Scheitelwerte der Beanspruchung.

Die folgende Arbeit enthält eine Theorie der Schwingungen eines Systems unter einem vorübergehenden Anstoß. Der erste Paragraph enthält die theoretischen Grundlage. Der Hauptgedanke ist die spektrale Zerlegung des Seismogramms, d. h. es wird die Frequenzverteilung des Erdstoßes untersucht. Dann ist es ziemlich einfach, die Wirkung eines solchen Stoßes auf ein Gebäude zu ermitteln.

Im zweiten Paragraphen wird diese Methode auf die Untersuchung der Erdbebensicherheit eines Gebäudes angewendet, das einen elastischen ersten Stock hat. Eine Tabelle ermöglicht die Berechnung der Schwingungsperioden des Gebäudes. Als Endergebnis erhält man die durch die Elastizität des ersten Stockwerks hervorgerufene Verringerung der Beanspruchungen.
Foreword: Mitochondrial Medicine
Authors: Murri Luigi
Published: May 2007

Mitochondrion is currently known to play major roles in many disease processes: neuromuscular disorders, neurodegenerative conditions (i.e. Parkinson's and Alzheimer's diseases), diabetes mellitus, aging, programmed cell death, and carcinogenesis, to name a few. In this background, the Department of Neuroscience of the University of Pisa (Italy) has organised a scientific meeting on October 25th, 2006, to discuss recent progress in the field of mitochondriology.
CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes
Authors: Nishida Takashi , Kawaki Harumi , Baxter Ruth M. , DeYoung R. Andrea , Takigawa Masaharu , Lyons Karen M.
Published: May 2007

The matricellular protein CCN2 (Connective Tissue Growth Factor; CTGF) is an essential mediator of ECM composition, as revealed through analysis of Ccn2 deficient mice. These die at birth due to complications arising from impaired endochondral ossification. However, the mechanism(s) by which CCN2 mediates its effects in cartilage are unclear. We investigated these mechanisms using Ccn2−/− chondrocytes. Expression of type II collagen and aggrecan were decreased in Ccn2−/− chondrocytes, confirming a defect in ECM production. Ccn2−/− chondrocytes also exhibited impaired DNA synthesis and reduced adhesion to fibronectin. This latter defect is associated with decreased expression of α5 integrin. Moreover, CCN2 can bind to integrin α5β1 in chondrocytes and can stimulate increased expression of integrin α5. Consistent with an essential role for CCN2 as a ligand for integrins, immunofluorescence and Western blot analysis revealed that levels of focal adhesion kinase (FAK) and extracellular signal‐regulated kinase (ERK)1/2 phosphorylation were reduced in Ccn2−/− chondrocytes. These findings argue that CCN2 exerts major effects in chondrocytes through its ability to (1) regulate ECM production and integrin α5 expression, (2) engage integrins and (3) activate integrin‐mediated signaling pathways.
A ‘practice of the variant’ and the origins of the standard. Presentation of a variationist linguistics method for a corpus of Old French charters
Authors: VÖLKER HARALD
Published: May 2007

Concerning the history of the linguistic standardisation of French, the period which begins with Louis XIV and the 17th century is well known and has been well documented. However, to the present day, discussions about the origins and the early periods of standardisation often suffer from a lack of intralinguistic evidence. The present article makes some suggestions which are designed to help compensate for this lack of evidence, and discusses some results from a German research project on Old French charters.
Part-of-speech tagging of Modern Hebrew text
Authors: BAR-HAIM ROY , SIMA'AN KHALIL , WINTER YOAD
Published: May 2007

Words in Semitic texts often consist of a concatenation ofword segments, each corresponding to a part-of-speech (POS) category. Semitic words may be ambiguous with regard to their segmentation as well as to the POS tags assigned to each segment. When designing POS taggers for Semitic languages, a major architectural decision concerns the choice of the atomic input tokens (terminal symbols). If the tokenization is at the word level, the output tags must be complex, and represent both the segmentation of the word and the POS tag assigned to each word segment. If the tokenization is at the segment level, the input itself must encode the different alternative segmentations of the words, while the output consists of standard POS tags. Comparing these two alternatives is not trivial, as the choice between them may have global effects on the grammatical model. Moreover, intermediate levels of tokenization between these two extremes are conceivable, and, as we aim to show, beneficial. To the best of our knowledge, the problem of tokenization for POS tagging of Semitic languages has not been addressed before in full generality. In this paper, we study this problem for the purpose of POS tagging of Modern Hebrew texts. After extensive error analysis of the two simple tokenization models, we propose a novel, linguistically motivated, intermediate tokenization model that gives better performance for Hebrew over the two initial architectures. Our study is based on the well-known hidden Markov models (HMMs). We start out from a manually devised morphological analyzer and a very small annotated corpus, and describe how to adapt an HMM-based POS tagger for both tokenization architectures. We present an effective technique for smoothing the lexical probabilities using an untagged corpus, and a novel transformation for casting the segment-level tagger in terms of a standard, word-level HMM implementation. The results obtained using our model are on par with the best published results on Modern Standard Arabic, despite the much smaller annotated corpus available for Modern Hebrew.
Calculating modules in contextual logic program refinement
Authors: COLVIN ROBERT , HAYES IAN J. , STROOPER PAUL
Published: May 2007

The refinement calculus for logic programs is a framework for deriving logic programs from specifications. It is based on a wide-spectrum language that can express both specifications and code, and a refinement relation that models the notion of correct implementation. In this paper we extend and generalise earlier work oncontextual refinement. Contextual refinement simplifies the refinement process by abstractly capturing the context of a subcomponent of a program, which typically includes information about the values of the free variables. This paper also extends and generalisesmodule refinement. Amoduleis a collection of procedures that operate on a common data type; module refinement between a specification moduleAand an implementation moduleCallows calls to the procedures ofAto be systematically replaced with calls to the corresponding procedures ofC. Based on the conditions for module refinement, we present a method forcalculatingan implementation module from a specification module. Both contextual and module refinement within the refinement calculus have been generalised from earlier work and the results are presented in a unified framework.
Thermal technique for controlling hydraulic fractures
Authors: Wu Ruiting , Germanovich Leonid N. , Van Dyke Peter E. , Lowell Robert P.
Published: May 2007

A simple technique is introduced to control hydraulic fractures in laboratory samples. This is achieved by heating or cooling samples prior to injecting the fracturing liquid, so that the induced thermal stresses govern the fracture orientation. We developed a simple theoretical model to parameterize experiments in laboratory settings and for materials that are different from ours. We also illustrate the utility of the technique with two examples: (1) mixed mode I+III hydraulic fracture propagation and (2) visualization of the fluid flow in the created fracture. In some cases, a similar technique may also be applicable for controlling the orientation of hydraulic fractures in field conditions.
Variability of the atmospheric circulation in the southern hemisphere during the last glacial maximum
Authors: Drost F. , Renwick J. , Bhaskaran B. , Oliver H. , McGregor J.
Published: May 2007

A high‐resolution atmospheric climate model has been used to investigate short‐term variability of the atmospheric circulation in the Southern Hemisphere during the Last Glacial Maximum (LGM). The model was forced at the lower boundary by sea surface temperatures (SSTs) and sea ice fields from a lower‐resolution coupled model simulation of the LGM. Although the semiannual oscillation (SAO) in the control simulation showed a different annual cycle than in the National Centers for Environmental Prediction (NCEP) reanalysis, the LGM SAO was similar to that of today, albeit slightly weaker, with the onset of the second peak delayed by a month. Nearly one third of the interannual variability of monthly mean 500‐hPa height anomalies was accounted for by the Southern Annular Mode. Empirical orthogonal function analysis showed that the next two most important modes looked similar to those associated with El Niño‐Southern Oscillation (ENSO). However, correlations of the associated time series with those of the coupled model's tropical sea surface SSTs were much smaller than for the observed present‐day ENSO correlations.
Scrubbing process and chemical equilibria controlling the composition of light hydrocarbons in natural gas discharges: An example from the geothermal fields of El Salvador
Authors: Tassi F. , Vaselli O. , Capaccioni B. , Montegrossi G. , Barahona F. , Caprai A.
Published: May 2007

The compositional features of fluids from both fumarolic discharges and productive geothermal wells of Ahuachapan‐Chipilapa, Berlin‐Chinameca, and San Vicente geothermal systems (El Salvador) are described and discussed in order to investigate the complex geochemical interactions involving geothermal fluids within the shallowest part of the hydrothermal circulation pathways. Our results highlight that secondary processes are able to strongly affect and modify the chemical characteristics of geothermal gases once they discharge to the surface as natural manifestations, mainly in relation to the chemical‐physical properties of each gas species. The effects of both gas dissolution in shallow aquifers and gas‐water‐rock chemical interactions on gas discharge composition make it difficult to get a correct evaluation of the thermodynamic conditions that characterize the geothermal reservoirs by applying the common geoindicators based on the chemical equilibria of the H2O‐CO2‐H2‐CH4‐CO system. Differently, the composition of the C1‐C2‐C3 alkanes and the C3 and C4 alkane‐alkene pair, established within the geothermal reservoirs under the control of chemical reactions, remains stable in samples collected from discharging gas vents. These results suggest that the relative abundances of hydrocarbons characterized by similar structure and molecular size seem to be mainly regulated by the diffusion velocity of gases through the liquid‐dominated system. Therefore the chemical features of the light organic gas fraction of naturally discharging fluids can be successfully utilized for the evaluation of geothermal reservoir temperatures and redox conditions, providing useful indications in terms of geothermal exploration and exploitation. On this basis, the distribution, speciation, and relative abundances of light hydrocarbons can also be considered highly promising in geochemical monitoring of active volcanic systems.
Effective elastic thickness of South America and its implications for intracontinental deformation
Authors: Pérez‐Gussinyé M. , Lowry A. R. , Watts A. B.
Published: May 2007

The flexural rigidity or effective elastic thickness of the lithosphere, Te, primarily depends on its thermal gradient and composition. Consequently, maps of the lateral variability of Te in continents reflect their lithospheric structure. We present here a new Te map of South America generated using a compilation of satellite‐derived (GRACE and CHAMP missions) and terrestrial gravity data (including EGM96 and SAGP), and a multitaper Bouguer coherence technique. Our Te maps correlate remarkably well with other proxies for lithospheric structure: areas with high Te have, in general, high lithospheric mantle shear wave velocity and low heat flow and vice versa. In this paper we focus on the Te of the stable platform. We find that old cratonic nuclei (mainly Archean and Early/Middle Proterozoic) have, in general, high Te (>70 km), while the younger Patagonian Phanerozoic terrane has much lower Te (20–30 km), suggesting that Te is related to terrane age as has already been noted in Europe. Within cratonic South America, Te variations are observed at regional scale: relatively lower Te occurs at sites that have been repeatedly reactivated throughout geological history as major sutures, rift zones, and sites of hot spot magmatism. Today, these low Te areas are surrounded by large cratonic nuclei. They concentrate most of the intracontinental seismicity and exhibit relatively high surface heat flow and low seismic velocity at 100 km depth. This implies that intracontinental deformation focuses within relatively thin, hot, and hence weak lithosphere, that cratonic interiors are strong enough to inhibit tectonism, and that the differences in lithospheric rigidity, structure, and composition between stable cratons and sites of intracontinental deformation are not transient, and may have been maintained, in some cases, for at least 500 m.y.
The whitecap coverage model from breaking dissipation parametrizations of wind waves
Authors: Guan Changlong , Hu Wei , Sun Jian , Li Ruili
Published: May 2007

An analytical model for whitecap coverage has been established from wave breaking dissipation models by improving the model of Kraan et al. [1996]. The similarity of three wave breaking parametrizations has been discussed and applied to develop the analytical model. The proposed model predicts an inversely quadratic dependence of whitecap coverage on wave age, after invoking the 3/2 power law. The undetermined parameter in the model is fixed with the latest published data sets. The proposed model is more consistent with the four data sets used than the other two analytical models presented more recently, which would underestimate significantly the four data sets overall. The substantiation of the field observations to inversely quadratic dependence on wave age means that the choice for the dependence of the damping rate on wave steepness by Komen et al. [1984] in quasilinear dissipation model has some support from observations of the whitecap coverage. The limitation of the single parameter description to whitecap coverage and the controversy on the nature of the dependence of wave breaking properties on wind wave status due to the single‐parameter description are discussed. It is pointed out that the multiple‐parameter scheme is expected to give rise to a consistent interpretation to the variability of whitecap coverage.
Seasonal and spatial variations in methyl chloride in NW Atlantic waters
Authors: MacDonald S. , Moore R. M.
Published: May 2007

Methyl chloride concentrations were measured in the upper 200 m of the water column of the NW Atlantic during three cruises along the same track in spring, summer and fall of 2003. Distinct seasonality was apparent, with the surface waters being either undersaturated or close to equilibrium with the atmosphere in spring, but with supersaturation of the warmer waters in summer and fall. Cooler waters at the more northerly stations were always undersaturated, thus representing a continual sink for atmospheric methyl chloride. Even on an annual basis, the concentration anomaly (the difference between measured concentration and equilibrium with the atmosphere) was strongly dependent on sea surface temperature (SST). This empirical relationship can be used to extrapolate fluxes globally or to estimate the influence of global warming on ocean‐to‐atmosphere fluxes of methyl chloride. The global flux of methyl chloride to the atmosphere estimate based on the full‐year relationship between concentration anomaly and SST is 17 Gmol/y, and is reduced to 6 Gmol/y if separate seasonal relationships are used. It appears that the ocean component of the flux is highly sensitive to temperature, but the actual source of the methyl chloride in ocean waters remains largely unknown.
Importance of the polarization in the retrieval of oceanic constituents from the remote sensing reflectance
Authors: Chami Malik
Published: May 2007

The influence of marine particles on the polarized radiation exiting the ocean is studied, and the implications for the retrieval of particulate concentration from remotely sensed data are investigated. Simulations were carried out using a vector radiative transfer model. Open ocean and coastal waters conditions were examined separately. In phytoplankton dominated waters, the polarized reflectance is virtually insensitive to the variations in chlorophyll concentration when observing at the top of atmosphere. The polarization effects induced by phytoplankton cells are too weak compared to those induced by the air‐water interface and the atmospheric particles (especially molecules) to significantly contribute to the polarized reflectance at this level of atmosphere. The use of the polarized information at short wavelengths is thus proposed to improve the retrieval of the spectral variation of the aerosol model in atmospheric correction algorithms. In coastal zones, the sensitivity of the polarized signal to the water content is much greater. The analysis demonstrates that the measurement of the polarized reflectance just above the sea surface may not be relevant to reduce the skylight reflection effects when the water mass is mainly dominated by highly refractive particles. It is shown that polarization measurements can be of great interest to separate the fraction of inorganic particles from biogenic cells. This study also highlights that an empirical‐based inversion approach relying on the polarized reflectance measured in the green and at longer wavelengths could be efficient to retrieve the concentration of inorganic particles regardless of the phytoplankton content in coastal waters.
Retrieval of average CO2 fluxes by combining in situ CO2 measurements and backscatter lidar information
Authors: Gibert Fabien , Schmidt Martina , Cuesta Juan , Ciais Philippe , Ramonet Michel , Xueref Irène , Larmanou Eric , Flamant Pierre Henri
Published: May 2007

The present paper deals with a boundary layer budgeting method which makes use of observations from various in situ and remote sensing instruments to infer regional average net ecosystem exchange (NEE) of CO2. Measurements of CO2 within and above the atmospheric boundary layer (ABL) by in situ sensors, in conjunction with a precise knowledge of the change in ABL height by lidar and radiosoundings, enable to infer diurnal and seasonal NEE variations. Near‐ground in situ CO measurements are used to discriminate natural and anthropogenic contributions of CO2 diurnal variations in the ABL. The method yields mean NEE that amounts to 5 μmol m−2 s−1 during the night and −20 μmol m−2 s−1 in the middle of the day between May and July. A good agreement is found with the expected NEE accounting for a mixed wheat field and forest area during winter season, representative of the mesoscale ecosystems in the Paris area according to the trajectory of an air column crossing the landscape. Daytime NEE is seen to follow the vegetation growth and the change in the ratio diffuse/direct radiation. The CO2 vertical mixing flux during the rise of the atmospheric boundary layer is also estimated and seems to be the main cause of the large decrease of CO2 mixing ratio in the morning. The outcomes on CO2 flux estimate are compared to eddy‐covariance measurements on a barley field. The importance of various sources of error and uncertainty on the retrieval is discussed. These errors are estimated to be less than 15%; the main error resulted from anthropogenic emissions.
Noise‐induced vegetation patterns in fire‐prone savannas
Authors: D'Odorico Paolo , Laio Francesco , Porporato Amilcare , Ridolfi Luca , Barbier Nicolas
Published: May 2007

The high degree of spatial organization of dryland vegetation has been often explained invoking a number of different deterministic mechanisms without ever explicitly addressing the role of noise in the process of pattern formation. Noise is usually believed to act on ecosystems as a source of disorganized random fluctuations. However, noise is also known for its ability to induce ordered states in nonlinear systems. An alternative mechanism is here proposed, which explains vegetation pattern formation in mesic and subhumid savannas as the joint effect of fire randomness and fire‐vegetation feedbacks. This mechanism is purely noise‐induced and has no deterministic counterpart.
Photosynthetically active radiation from Clouds and the Earth's Radiant Energy System (CERES) products
Authors: Su Wenying , Charlock Thomas P. , Rose Fred G. , Rutan David
Published: May 2007

We describe a method that retrieves surface photosynthetically active radiation (PAR) and its direct and diffuse components from the Surface and Atmospheric Radiation Budget (SARB) product of Clouds and the Earth's Radiant Energy System (CERES). The shortwave spectrum in the SARB Edition 2 is calculated in 15 bands, 4 of which are used to develop the PAR, in conjunction with the look‐up tables described in this paper. We apply these look‐up tables to existing CERES Terra Edition 2 products. The new retrieved surface PAR is validated with LI‐COR PAR measurements at seven Surface Radiation Budget Network (SURFRAD) sites using data from March 2000 to June 2005. The relative bias of retrieved all‐sky PAR at the SURFRAD sites is 4.6% (positive sign indicating retrieval exceeds measurement), and 54% of the all‐sky samples are within the ±10% uncertainty of the LI‐COR PAR measurements. The satellite field‐of‐view (FOV) is more representative of the ground instrument FOV under clear conditions, so 89% of clear‐sky retrievals are within the uncertainty of the LI‐COR PAR measurements at SURFRAD sites with positive biases at most sites. The retrieved PAR is also validated at the Atmospheric Radiation Measurement (ARM) Southern Great Plains Central Facility (CF) site using data from October 2003 to June 2004 for those FOVs having both LI‐COR and Rotating Shadowband Spectroradiometer (RSS) ground measurements; for this small domain, all‐sky relative biases are again positive (1.9%) for LI‐COR but negative (−4.2%) for RSS. The direct‐to‐diffuse ratio derived from CERES is smaller than that from RSS for both clear and cloudy conditions. CERES also retrieves the broadband shortwave insolation, and the relative biases for the broadband retrievals are much less than those for PAR at the above sites. It appears that some of the ground‐based measurements of PAR do not have the fidelity of those for broadband shortwave insolation.
Dynamics of nutrients and oxygen/hydrogen sulfide in the Baltic Sea deep water
Authors: Gustafsson Bo G. , Stigebrandt Anders
Published: May 2007

The water in the deepest basins of the Baltic Sea is only intermittently renewed. The interval between water renewals, so‐called stagnation periods, are typically several years during which only turbulent diffusive exchange of matter occurs with overlying water. The diffusive fluxes of nutrients, oxygen, and hydrogen sulfide through the 150‐m level in the Eastern Gotland deep basin were computed from high‐quality hydrographic and hydrochemical observations. Comparing diffusive fluxes with observed storage changes in the basin water, the residual corresponding to the net source or sink due to biogeochemical transformations could be obtained. It is found that decomposition rates of organic matter vary by a factor of about 3.5 mostly owing to variations in redox conditions. On average, 15.8 gC m−2 yr−1 are decomposed in the deep basin. No trend is found in the investigated period 1965–2005. The variability of the phosphate source is dominated by release of dissolved phosphate from particulate iron‐bound phosphate at oxic to anoxic transitions. It is found that the deep sediments release about 3 gP m−2 when overlying water turns anoxic. Denitrification rates are on average 2.6 gN m−2 yr−1, but also these are highly variable depending on redox conditions. By adding observed organic matter accumulation in the sediments to the estimated organic matter decomposition, we conclude that the supply of organic matter through the 150 m horizon is about 30.6 gC m−2 yr−1. Further, the results corroborate that the nutrient content of the organic matter supply follows approximately the Redfield ratio.
Thorium‐230 normalized particle flux and sediment focusing in the Panama Basin region during the last 30,000 years
Authors: Kienast S. S. , Kienast M. , Mix A. C. , Calvert S. E. , François R.
Published: May 2007

Application of the 230Th normalization method to estimate sediment burial fluxes in six cores from the eastern equatorial Pacific (EEP) reveals that bulk sediment and organic carbon fluxes display a coherent regional pattern during the Holocene that is consistent with modern oceanographic conditions, in contrast with estimates of bulk mass accumulation rates (MARs) derived from core chronologies. Two nearby sites (less than 10 km apart), which have different MARs, show nearly identical 230Th‐normalized bulk fluxes. Focusing factors derived from the 230Th data at the foot of the Carnegie Ridge in the Panama Basin are >2 in the Holocene, implying that lateral sediment addition is significant in this part of the basin. New geochemical data and existing literature provide evidence for a hydrothermal source of sediment in the southern part of the Panama Basin and for downslope transport from the top of the Carnegie Ridge. The compilation of core records suggests that sediment focusing is spatially and temporally variable in the EEP. During oxygen isotope stage 2 (OIS 2, from 13–27 ka BP), focusing appears even higher compared to the Holocene at most sites, similar to earlier findings in the eastern and central equatorial Pacific. The magnitude of the glacial increase in focusing factors, however, is strongly dependent on the accuracy of age models. We offer two possible explanations for the increase in glacial focusing compared to the Holocene. The first one is that the apparent increase in lateral sediment redistribution is partly or even largely an artifact of insufficient age control in the EEP, while the second explanation, which assumes that the observed increase is real, involves enhanced deep sea tidal current flow during periods of low sea level stand.
Role of topography in isotherm perturbation: Apatite (U‐Th)/He and fission track results from the Malta tunnel, Tauern Window, Austria
Authors: Foeken Jurgen P. T. , Persano Cristina , Stuart Finlay M. , ter Voorde Marlies
Published: May 2007

Apatite (U‐Th)/He and fission track age determinations of samples from a 20‐km‐long, near‐horizontal tunnel in the Hochalm‐Ankogel Dome (eastern Tauern Window, Austria) are presented in order to determine the role of (paleo)‐topography in perturbing isotherms in the shallow crust. Apatite fission track ages (26–8 Ma) show no systematic correlation with distance along the tunnel or elevation. Two age components in the fission track data indicate cooling through ∼120°C at approximately 20 Ma and ∼80°C at approximately 6 Ma. Surface and tunnel (U‐Th)/He ages (17–9 Ma and 13–5 Ma, respectively) are consistently younger than the equivalent fission track ages. (U‐Th)/He ages vary systematically along the tunnel with older ages at the northern and southern tunnel portals and younger ages in the central section. Geological factors (faulting, lithology) appear to have had little effect on this age distribution. The (U‐Th)/He age pattern is inconsistent with rock cooling underneath the present‐day Hochalm‐Ankogel Dome topography. The age minimum is interpreted to coincide with a paleotopographic maximum in the Hochalm‐Ankogel Dome and suggests that the 40–60°C isotherms were warped sufficiently to affect apatite (U‐Th)/He ages. The tunnel apatite (U‐Th)/He ages match synthetic He ages derived from a two‐dimensional numerical model of landscape evolution. Integrating the thermal model results with the data allows the relief development to be constrained and we calculate that the present‐day Hochalm‐Ankogel Dome topography was formed at 7 to 10 Ma.
Insulin-induced formation of macromolecular complexes involved in activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and its interaction with PKB
Authors: Ahmad Faiyaz , Lindh Rebecka , Tang Yan , Weston Marie , Degerman Eva , Manganiello Vincent C.
Published: May 2007

Fractionation of 3T3-L1 adipocyte membranes revealed that PDE3B (phosphodiesterase 3B) was associated with PM (plasma membrane) and ER (endoplasmic reticulum)/Golgi fractions, that insulin-induced phosphorylation/activation of PDE3B was greater in internal membranes than PM fractions, and that there was no significant translocation of PDE3B between membrane fractions. Insulin also induced formation of large macromolecular complexes, separated during gel filtration (Superose 6 columns) of solubilized membranes, which apparently contain phosphorylated/activated PDE3B and signalling molecules potentially involved in its activation by insulin, e.g. IRS-1 (insulin receptor substrate-1), IRS-2, PI3K p85 [p85-subunit of PI3K (phosphoinositide 3-kinase)], PKB (protein kinase B), HSP-90 (heat-shock protein 90) and 14-3-3. Expression of full-length recombinant FLAG-tagged murine (M) PDE3B and M3BΔ604 (MPDE3B lacking N-terminal 604 amino acids) indicated that the N-terminal region of MPDE3B was necessary for insulin-induced activation and recruitment of PDE3B. siRNA (small interfering RNA) knock-down of PDE3B indicated that PDE3B was not required for formation of insulin-induced complexes. Wortmannin inhibited insulin-induced assembly of macromolecular complexes, as well as phosphorylation/activation of PKB and PDE3B, and their co-immunoprecipitation. Another PI3K inhibitor, LY294002, and the tyrosine kinase inhibitor, Genistein, also inhibited insulin-induced activation of PDE3B and its co-immunoprecipitation with PKB. Confocal microscopy indicated co-localization of PDE3B and PKB. Recombinant MPDE3B co-immunoprecipitated, and co-eluted during Superose 12 chromatography, to a greater extent with recombinant pPKB (phosphorylated/activated PKB) than dephospho-PKB or p-ΔPKB [pPKB lacking its PH domain (pleckstrin homology domain)]. Truncated recombinant MPDE3B proteins and pPKB did not efficiently co-immunoprecipitate, suggesting that structural determinants for their interaction reside in, or are regulated by, the N-terminal portion of MPDE3B. Recruitment of PDE3B in macromolecular complexes may be critical for regulation of specific cAMP pools and signalling pathways by insulin, e.g. lipolysis.
Regulation of oncogenic transcription factor hTAFII68-TEC activity by human glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
Authors: Kim Sol , Lee Jungwoon , Kim Jungho
Published: May 2007

Tumour-specific chromosomal rearrangements are known to create chimaeric products with the ability to generate many human cancers. hTAFII68-TEC (where hTAFII68 is human TATA-binding protein-associated factor II 68 and TEC is translocated in extraskeletal chondrosarcoma) is such a fusion product, resulting from a t(9;17) chromosomal translocation found in extraskeletal myxoid chondrosarcomas, where the hTAFII68 NTD (N-terminal domain) is fused to TEC protein. To identify proteins that control hTAFII68-TEC function, we used affinity chromatography on immobilized hTAFII68 (NTD) and MALDI-TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS and isolated a novel hTAFII68-TEC-interacting protein, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). GAPDH is a glycolytic enzyme that is also involved in the early steps of apoptosis, nuclear tRNA export, DNA replication, DNA repair and transcription. hTAFII68-TEC and GAPDH were co-immunoprecipitated from cell extracts, and glutathione S-transferase pull-down assays revealed that the C-terminus of hTAFII68 (NTD) was required for interaction with GAPDH. In addition, three independent regions of GAPDH (amino acids 1–66, 67–160 and 160–248) were involved in binding to hTAFII68 (NTD). hTAFII68-TEC-dependent transcription was enhanced by GAPDH, but not by a GAPDH mutant defective in hTAFII68-TEC binding. Moreover, a fusion of GAPDH with the GAL4 DNA-binding domain increased the promoter activity of a reporter containing GAL4 DNA-binding sites, demonstrating the presence of a transactivation domain(s) in GAPDH. The results of the present study suggest that the transactivation potential of the hTAFII68-TEC oncogene product is positively modulated by GAPDH.
Regulation and functional consequences of ADP receptor-mediated ERK2 activation in platelets
Authors: Garcia Analia , Shankar Haripriya , Murugappan Swaminathan , Kim Soochong , Kunapuli Satya P.
Published: May 2007

We have previously shown that ADP-induced thromboxane generation in platelets requires signalling events from the Gq-coupled P2Y1 receptor (platelet ADP receptor coupled to stimulation of phospholipase C) and the Gi-coupled P2Y12 receptor (platelet ADP receptor coupled to inhibition of adenylate cyclase) in addition to outside-in signalling. While it is also known that extracellular calcium negatively regulates ADP-induced thromboxane A2 generation, the underlying mechanism remains unclear. In the present study we sought to elucidate the signalling mechanisms and regulation by extracellular calcium of ADP-induced thromboxane A2 generation in platelets. ERK (extracllular-signal-regulated kinase) 2 activation occurred when outside-in signalling was blocked, indicating that it is a downstream event from the P2Y receptors. However, blockade of either P2Y1 or the P2Y12 receptors with corresponding antagonists completely abolished ERK phosphorylation, indicating that both P2Y receptors are required for ADP-induced ERK activation. Inhibitors of Src family kinases or the ERK upstream kinase MEK [MAPK (mitogen-activated protein kinase)/ERK kinase] abrogated ADP-induced ERK phosphorylation and thromboxane A2 generation. Finally ADP- or Gi+Gz-induced ERK phosphorylation was blocked in the presence of extracellular calcium. The present studies show that ERK2 is activated downstream of P2Y receptors through a complex mechanism involving Src kinases and this plays an important role in ADP-induced thromboxane A2 generation. We also conclude that extracellular calcium blocks ADP-induced thromboxane A2 generation through the inhibition of ERK activation.
Were inefficient mitochondrial haplogroups selected during migrations of modern humans? A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines
Authors: Amo Taku , Brand Martin D.
Published: May 2007

We introduce a general test of the bioenergetic importance of mtDNA (mitochondrial DNA) variants: modular kinetic analysis of oxidative phosphorylation in mitochondria from cybrid cells with constant nuclear DNA but different mtDNA. We have applied this test to the hypothesis [Ruiz-Pesini, Mishmar, Brandon, Procaccio and Wallace (2004) Science 303, 223–226] that particular mtDNA haplogroups (specific combinations of polymorphisms) that cause lowered coupling efficiency, leading to generation of less ATP and more heat, were positively selected during radiations of modern humans into colder climates. Contrary to the predictions of this hypothesis, mitochondria from Arctic haplogroups had similar or even greater coupling efficiency than mitochondria from tropical haplogroups.
Inhibition of PDGF-BB by Factor VII-activating protease (FSAP) is neutralized by protease nexin-1, and the FSAP–inhibitor complexes are internalized via LRP
Authors: Muhl Lars , Nykjaer Anders , Wygrecka Malgorzata , Monard Denis , Preissner Klaus T. , Kanse Sandip M.
Published: May 2007

FSAP (Factor VII-activating protease) can inhibit neointima formation and VSMC (vascular smooth-muscle cell) proliferation by cleavage of PDGF-BB (platelet-derived growth factor-BB). Negatively charged polyanions lead to autoactivation of the FSAP, but no information is available concerning the potential regulation of FSAP activity and its metabolism in the vessel wall. In the present study, we demonstrate that the enzymatic activity of FSAP can be inhibited by the serine protease inhibitor, PN-1 (protease nexin-1), that is found in the vasculature. This leads to the loss of the inhibitory effect of FSAP on PDGF-BB-mediated DNA synthesis and mitogen-activated protein kinase phosphorylation in VSMCs. The FSAP–PN-1 complexes bind to the LRP (low-density lipoprotein receptor-related protein) and are subsequently internalized. This binding is inhibited by receptor-associated protein, an antagonist of LRP, as well as heparin. While PDGFβR (PDGFβ receptor) is internalized by an LRP-dependent mechanism after stimulation of cells by PDGF-BB, the FSAP–PN-1 complex neither influenced PDGF-BB-mediated phosphorylation of PDGFβR nor its internalization via LRP. Hence, PN-1 inhibits the enzymatic activity of FSAP and neutralizes its effect on PDGF-BB-mediated VSMC proliferation. The FSAP–inhibitor complexes are internalized via LRP without influencing the PDGF-BB signal transduction pathway.
Molecular mechanisms involved in the regulation of cytokine production by muramyl dipeptide
Authors: Windheim Mark , Lang Christine , Peggie Mark , Plater Lorna A. , Cohen Philip
Published: May 2007

MDP (muramyl dipeptide), a component of peptidoglycan, interacts with NOD2 (nucleotide-binding oligomerization domain 2) stimulating the NOD2–RIP2 (receptor-interacting protein 2) complex to activate signalling pathways important for antibacterial defence. Here we demonstrate that the protein kinase activity of RIP2 has two functions, namely to limit the strength of downstream signalling and to stabilize the active enzyme. Thus pharmacological inhibition of RIP2 kinase with either SB 203580 [a p38 MAPK (mitogen-activated protein kinase) inhibitor] or the Src family kinase inhibitor PP2 induces a rapid and drastic decrease in the level of the RIP2 protein, which may explain why these RIP2 inhibitors block MDP-stimulated downstream signalling and the production of IL-1β (interleukin-1β) and TNFα (tumour necrosis factor-α). We also show that RIP2 induces the activation of the protein kinase TAK1 (transforming-growth-factor-β-activated kinase-1), that a dominant-negative mutant of TAK1 inhibits RIP2-induced activation of JNK (c-Jun N-terminal kinase) and p38α MAPK, and that signalling downstream of NOD2 or RIP2 is reduced by the TAK1 inhibitor (5Z)-7-oxozeaenol or in TAK1-deficient cells. We also show that MDP activates ERK1 (extracellular-signal-regulated kinase 1)/ERK2 and p38α MAPK in human peripheral-blood mononuclear cells and that the activity of both MAPKs and TAK1 are required for MDP-induced signalling and production of IL-1β and TNFα in these cells. Taken together, our results indicate that the MDP–NOD2/RIP2 and LPS (lipopolysaccharide)–TLR4 (Toll-like receptor 4) signalling pathways converge at the level of TAK1 and that many subsequent events that lead to the production of pro-inflammatory cytokines are common to both pathways.
Citrinin induces apoptosis via a mitochondria-dependent pathway and inhibition of survival signals in embryonic stem cells, and causes developmental injury in blastocysts
Authors: Chan Wen-Hsiung
Published: May 2007

The mycotoxin CTN (citrinin), a natural contaminant in foodstuffs and animal feeds, has cytotoxic and genotoxic effects on various mammalian cells. CTN is known to cause cell injury, including apoptosis, but the precise regulatory mechanisms of CTN action, particularly in stem cells and embryos, are currently unclear. In the present paper, I report that CTN has cytotoxic effects on mouse embryonic stem cells and blastocysts, and is associated with defects in their subsequent development, both in vitro and in vivo. Experiments in embryonic stem cells (ESC-B5) showed that CTN induces apoptosis via ROS (reactive oxygen species) generation, increased Bax/Bcl-2 ratio, loss of MMP (mitochondrial membrane potential), induction of cytochrome c release, and activation of caspase 3. In this model, CTN triggers cell death via inactivation of the HSP90 [a 90 kDa isoform of the HSP (heat-shock protein) family proteins]/multichaperone complex and subsequent degradation of Ras and Raf-1, further inhibiting anti-apoptotic processes, such as the Ras→ERK (extracellular-signal-regulated kinase) signal transduction pathway. In addition, CTN causes early developmental injury in mouse ESCs and blastocysts in vitro. Lastly, using an in vivo mouse model, I show that consumption of drinking water containing 10 μM CTN results in blastocyst apoptosis and early embryonic developmental injury. Collectively, these findings show for the first time that CTN induces ROS and mitochondria-dependent apoptotic processes, inhibits Ras→ERK survival signalling via inactivation of the HSP90/multichaperone complex, and causes developmental injury in vivo.
A proline repeat domain in the Notch co-activator MAML1 is important for the p300-mediated acetylation of MAML1
Authors: Saint Just Ribeiro Mariana , Hansson Magnus L. , Wallberg Annika E.
Published: May 2007

Ligand activation of Notch leads to the release of Notch IC (the intracellular receptor domain), which translocates to the nucleus and interacts with the DNA-binding protein CSL to control expression of specific target genes. In addition to ligand-mediated activation, Notch signalling can be further modulated by interactions of Notch IC with a number of other proteins. MAML1 has previously been shown to act co-operatively with the histone acetyltransferase p300 in Notch IC-mediated transcription. In the present study we show that the N-terminal domain of MAML1 directly interacts with both p300 and histones, and the p300–MAML1 complex specifically acetylates histone H3 and H4 tails in chromatin. Furthermore, p300 acetylates MAML1 and evolutionarily conserved lysine residues in the MAML1 N-terminus are direct substrates for p300-mediated acetylation. The N-terminal domain of MAML1 contains a proline repeat motif (PXPAAPAP) that was previously shown to be present in p53 and important for the p300–p53 interaction. We show that the MAML1 proline repeat motif interacts with p300 and enhances the activity of the MAML1 N-terminus in vivo. These findings suggest that the N-terminal domain of MAML1 plays an important role in Notch-regulated transcription, by direct interactions with Notch, p300 and histones.
The role of Tyr605 and Ala607 of thimet oligopeptidase and Tyr606 and Gly608 of neurolysin in substrate hydrolysis and inhibitor binding
Authors: Machado Maurício F. M. , Rioli Vanessa , Dalio Fernanda M. , Castro Leandro M. , Juliano Maria A. , Tersariol Ivarne L. , Ferro Emer S. , Juliano Luiz , Oliveira Vitor
Published: May 2007

The physicochemical properties of TOP (thimet oligopeptidase) and NEL (neurolysin) and their hydrolytic activities towards the FRET (fluorescence resonance energy transfer) peptide series Abz-GFSXFRQ-EDDnp [where Abz is o-aminobenzoyl; X=Ala, Ile, Leu, Phe, Tyr, Trp, Ser, Gln, Glu, His, Arg or Pro; and EDDnp is N-(2,4-dinitrophenyl)-ethylenediamine] were compared with those of site-mutated analogues. Mutations at Tyr605 and Ala607 in TOP and at Tyr606 and Gly608 in NEL did not affect the overall folding of the two peptidases, as indicated by their thermal stability, CD analysis and the pH-dependence of the intrinsic fluorescence of the protein. The kinetic parameters for the hydrolysis of substrates with systematic variations at position P1 showed that Tyr605 and Tyr606 of TOP and NEL respectively, played a role in subsite S1. Ala607 of TOP and Gly608 of NEL contributed to the flexibility of the loops formed by residues 600–612 (GHLAGGYDGQYYG; one-letter amino acid codes used) in NEL and 599–611 (GHLAGGYDAQYYG; one-letter amino acid codes used) in TOP contributing to the distinct substrate specificities, particularly with an isoleucine residue at P1. TOP Y605A was inhibited less efficiently by JA-2 {N-[1-(R,S)-carboxy-3-phenylpropyl]Ala-Aib-Tyr-p-aminobenzoate}, which suggested that the aromatic ring of Tyr605 was an important anchor for its interaction with wild-type TOP. The hydroxy groups of Tyr605 and Tyr606 did not contribute to the pH-activity profiles, since the pKs obtained in the assays of mutants TOP Y605F and NEL Y606F were similar to those of wild-type peptidases. However, the pH–kcat/Km dependence curve of TOP Y605A differed from that of wild-type TOP and from TOP Y606F. These results provide insights into the residues involved in the substrate specificities of TOP and NEL and how they select cytosolic peptides for hydrolysis.