bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferential chemosensitization of PTEN‐mutated prostate cells by silencing the Akt kinase
Authors: Priulla Marcella , Calastretti Angela , Bruno Paola , Amalia Azzariti , Paradiso Angelo , Canti Gianfranco , Nicolin Angelo
Published: March 2007

BACKGROUND

In prostate cancer, mutations of the phosphatase PTEN can activate the kinase cascade PI3K/Akt/mTOR which induces drug resistance.

METHODS

Chemosensitization by siRNA targeting Akt was studied in HEK293 cells forced to express CA‐Akt or kinase‐dead DN‐Akt. To decrease drug resistance, Akt was silenced with siRNA in human prostate DU‐145 cell line expressing the normal PTEN or in LNCaP and PC3 cell lines expressing mutated‐PTEN. Taxol was used for the chemosensitization studies.

RESULTS

Silencing Akt in the drug‐resistant CA‐Akt cells efficiently sensitized cells to antitubule agents, whereas silencing drug‐responsive DN‐Akt cells did not. Only minor effects were obtained in wild‐type HEK293 cells. Potentiation by siRNA of taxol cytotoxicity was significantly greater in mutated‐PTEN cells than in prostate cells expressing wild‐type PTEN. The apoptotic program induced by taxol was preferentially potentiated by Akt siRNA in PTEN‐mutated cell lines as regards the DU‐145 cell line.

CONCLUSIONS

Silencing Akt in PTEN‐mutated prostate cancer cells enhances the antitumor effects of taxol. No siRNA chemosensitization was obtained in prostate cells with wild type PTEN. Prostate 67: 782–789, 2007. © 2007 Wiley‐Liss, Inc.
High resolution structure of streptavidin in complex with a novel high affinity peptide tag mimicking the biotin binding motif
Authors: Perbandt M. , Bruns O. , Vallazza M. , Lamla T. , Betzel Ch. , Erdmann V.A.
Published: March 2007

A novel peptide was designed which possesses nanomolar affinity of less than 20 nM for streptavidin. Therefore it was termed Nano‐tag and has been used as an affinity tag for recombinant proteins. The minimized version of the wild type Nano‐tag is a seven‐amino acid peptide with the sequence fMDVEAWL. The three‐dimensional structure of wild type streptavidin in complex with the minimized Nano‐tag was analyzed at atomic resolution of 1.15 Å and the details of the binding motif were investigated. The peptide recognizes the same pocket of streptavidin where the natural ligand biotin is bound, but the peptide requires significantly more space than biotin. Therefore the binding loop adopts an “open” conformation in order to release additional space for the peptide. The conformation of the bound Nano‐tag corresponds to a 310 helix. However, the analysis of the intermolecular interactions of the Nano‐tag with residues of the binding pocket of streptavidin reveals astonishing similarities to the biotin binding motif. In principle the three‐dimensional conformation of the Nano‐tag mimics the binding mode of biotin. Our results explain why the use of the Nano‐tag in fusion with recombinant proteins is restricted to their N‐terminus and we describe the special significance of the fMet residue for the high affinity binding mode. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Attempt to simplify the amino‐acid sequence of photoactive yellow protein with a set of simple rules
Authors: Shirai Kumiko , Yamazaki Yoichi , Kamikubo Hironari , Imamoto Yasushi , Kataoka Mikio
Published: March 2007

To understand the information encoded in an amino‐acid sequence, the authors have attempted to simplify the amino‐acid sequence of photoactive yellow protein (PYP) with a set of simple rules. The rules are designed to reduce overlapping structural information. The simplified PYP protein, which was composed of only nine species of amino acids (Ser, Val, Asp, Lys, Phe, Met, Gly, Pro, and Cys), took a completely different structure than the native conformation. Even after the evolutionarily conserved residues were restored in the simplified protein, the PYP variant did not properly fold, indicating that the information encoded in the conserved residues is insufficient for the structure formation. Additional restorations of the substituted hydrophilic or hydrophobic residues did not lead to a variant that formed the native structure. The structural properties of these variants and the wild‐type protein in aqueous solution differed. Partial simplification was successfully performed by creating chimeric proteins composed of combinations of wild‐type PYP and sPYPIII. The structural characterization of each chimeric protein indicates that the important information on the structure formation is encoded in the β‐scaffold region. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Can molecular dynamics simulations provide high‐resolution refinement of protein structure?
Authors: Chen Jianhan , Brooks Charles L.
Published: March 2007

Recent advances in efficient and accurate treatment of solvent with the generalized Born approximation (GB) have made it possible to substantially refine the protein structures generated by various prediction tools through detailed molecular dynamics simulations. As demonstrated in a recent CASPR experiment, improvement can be quite reliably achieved when the initial models are sufficiently close to the native basin (e.g., 3–4 Å Cα RMSD). A key element to effective refinement is to incorporate reliable structural information into the simulation protocol. Without intimate knowledge of the target and prediction protocol used to generate the initial structural models, it can be assumed that the regular secondary structure elements (helices and strands) and overall fold topology are largely correct to start with, such that the protocol limits itself to the scope of refinement and focuses the sampling in vicinity of the initial structure. The secondary structures can be enforced by dihedral restraints and the topology through structural contacts, implemented as either multiple pair‐wise Cα distance restraints or a single sidechain distance matrix restraint. The restraints are weakly imposed with flat‐bottom potentials to allow sufficient flexibility for structural rearrangement. Refinement is further facilitated by enhanced sampling of advanced techniques such as the replica exchange method (REX). In general, for single domain proteins of small to medium sizes, 3–5 nanoseconds of REX/GB refinement simulations appear to be sufficient for reasonable convergence. Clustering of the resulting structural ensembles can yield refined models over 1.0 Å closer to the native structure in Cα RMSD. Substantial improvement of sidechain contacts and rotamer states can also be achieved in most cases. Additional improvement is possible with longer sampling and knowledge of the robust structural features in the initial models for a given prediction protocol. Nevertheless, limitations still exist in sampling as well as force field accuracy, manifested as difficulty in refinement of long and flexible loops. Proteins 2007. © 2007 Wiley‐Liss, Inc.
ZRANK: Reranking protein docking predictions with an optimized energy function
Authors: Pierce Brian , Weng Zhiping
Published: March 2007

Protein–protein docking requires fast and effective methods to quickly discriminate correct from incorrect predictions generated by initial‐stage docking. We have developed and tested a scoring function that utilizes detailed electrostatics, van der Waals, and desolvation to rescore initial‐stage docking predictions. Weights for the scoring terms were optimized for a set of test cases, and this optimized function was then tested on an independent set of nonredundant cases. This program, named ZRANK, is shown to significantly improve the success rate over the initial ZDOCK rankings across a large benchmark. The amount of test cases with No. 1 ranked hits increased from 2 to 11 and from 6 to 12 when predictions from two ZDOCK versions were considered. ZRANK can be applied either as a refinement protocol in itself or as a preprocessing stage to enrich the well‐ranked hits prior to further refinement. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Molecular adaptation strategies to high temperature and thermal denaturation mechanism of the D‐trehalose/D‐maltose‐binding protein from the hyperthermophilic archaeon Thermococcus litoralis
Authors: Fessas Dimitrios , Staiano Maria , Barbiroli Alberto , Marabotti Anna , Schiraldi Alberto , Varriale Antonio , Rossi Mose' , D'Auria Sabato
Published: March 2007

The D‐trehalose/D‐maltose‐binding protein (TMBP), a monomeric protein of 48 kDa, is one component of the trehalose and maltose uptake system. In the hyperthermophilic archaeon T. litoralis this is mediated by a protein‐dependent ATP‐binding cassette system transporter. The gene coding for a thermostable TMBP from the archaeon T. litoralis has been cloned, and the recombinant protein has been expressed in E. coli. The recombinant TMBP has been purified to homogeneity and characterized. It exhibits the same functional and structural properties as the native one. In fact, it is highly thermostable and binds both trehalose and maltose with high affinity. In this work we used differential scanning calorimetry studies together with a detailed analysis, at the molecular level, of the three‐dimensional protein structure to shed light on the basis of the high thermostability exhibited by the recombinant TMBP from the archaeon T. litoralis. The obtained data suggest that the presence of trehalose does not change the overall mechanism of the denaturation of this protein but it selectively modifies the stability of the TMBP structural domains. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Comparison between computational alanine scanning and per‐residue binding free energy decomposition for protein–protein association using MM‐GBSA: Application to the TCR‐p‐MHC complex
Authors: Zoete Vincent , Michielin Olivier
Published: March 2007

Recognition by the T‐cell receptor (TCR) of immunogenic peptides (p) presented by Class I major histocompatibility complexes (MHC) is the key event in the immune response against virus‐infected cells or tumor cells. A study of the 2C TCR/SIYR/H‐2Kb system using a computational alanine scanning and a much faster binding free energy decomposition based on the Molecular Mechanics—Generalized Born Surface Area (MM‐GBSA) method is presented. The results show that the TCR‐p‐MHC binding free energy decomposition using this approach and including entropic terms provides a detailed and reliable description of the interactions between the molecules at an atomistic level. Comparison of the decomposition results with experimentally determined activity differences for alanine mutants yields a correlation of 0.67 when the entropy is neglected and 0.72 when the entropy is taken into account. Similarly, comparison of experimental activities with variations in binding free energies determined by computational alanine scanning yields correlations of 0.72 and 0.74 when the entropy is neglected or taken into account, respectively. Some key interactions for the TCR‐p‐MHC binding are analyzed and some possible side chains replacements are proposed in the context of TCR protein engineering. In addition, a comparison of the two theoretical approaches for estimating the role of each side chain in the complexation is given, and a new ad hoc approach to decompose the vibrational entropy term into atomic contributions, the linear decomposition of the vibrational entropy (LDVE), is introduced. The latter allows the rapid calculation of the entropic contribution of interesting side chains to the binding. This new method is based on the idea that the most important contributions to the vibrational entropy of a molecule originate from residues that contribute most to the vibrational amplitude of the normal modes. The LDVE approach is shown to provide results very similar to those of the exact but highly computationally demanding method. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Malaria vector control in the third millennium: progress and perspectives of molecular approaches
Authors: Catteruccia Flaminia
Published: March 2007

Remarkable progress has been made towards a deeper understanding of mosquito biology since the completion of the Anopheles gambiae Giles genome project. Combined with the development of efficient transgenic technologies for genetic modification of major vector species and the availability of powerful molecular, genetic and bioinformatics tools, this is allowing the identification of genes involved in mosquito biological functions crucial to malaria transmission, ranging from host‐seeking behaviour and innate immunity to insecticide resistance. Moreover, population genetic studies are beginning to elucidate the complex structure of vector populations. Finally, novel methods for malaria control are emerging that are based on the use of genetically modified mosquitoes either to interrupt the journey of the Plasmodium parasite within its insect host or to suppress those mosquito species that function as vectors for parasite transmission. Copyright © 2007 Society of Chemical Industry
West Nile virus in North America: perspectives on epidemiology and intervention
Authors: Reisen William , Brault Aaron C
Published: March 2007

West Nile virus (WNV) invaded New York in 1999 and rapidly swept across the North American continent to the West Coast, north into southern Canada and south into Latin America, with minimal genetic change. Regional epidemics in equines and humans typically have included a year of viral introduction with minimal activity, successful overwintering, explosive amplification to epidemic levels the following year and then rapid subsidence. Overwintering possibly included long‐term mosquito or avian infections, continued low‐level transmission at southern latitudes and dispersal by south–north migrants. Explosive amplification has been associated with infections in several corvid species and other urban birds that produce elevated viremias capable of efficiently infecting even moderately susceptible mosquito species. Intervention has included mass vaccination of equines, and proactive and reactive mosquito control. Proactive mosquito control in areas with established infrastructure has been successful in reducing case incidence. Copyright © 2007 Society of Chemical Industry
Longitudinal‐electric‐field influence on Rochelle salt crystals
Authors: Moina A. P. , Slivka A. G. , Kedyulich V. M.
Published: March 2007

The influence of the longitudinal electric field on the static and dynamic dielectric, elastic, piezoelectric characteristics of Rochelle salt, as well as sound attenuation, is studied within the two‐sublattice Mitsui model taking into account the piezoelectric coupling. A satisfactory agreement with experimental data is obtained for the field effect on the static dielectric permittivity near the lower Curie temperature. At the upper Curie temperature an effective field should be used in calculations to describe the experiment. A possible role of space‐charge build‐up in screening of the external field at high temperatures is discussed. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Properties of nanoporous carbon with pores filled by Ni atoms
Authors: Shanina B. D. , Veynger A. , Danishevskii A. M. , Popov V. V. , Kyutt R. N. , Shuman V. B. , Kurdyukov D. A. , Gordeev S. K.
Published: March 2007

Using the electron spin resonance (ESR) method, conductance measurements, and small‐angle X‐ray scattering (SAXS), the properties of nanoporous carbon (NPC) containing atoms of Ni in the pores are studied in comparison with the nickel‐free NPC studied before. Although the amount of Ni introduced into the nanopores is small, the NPC properties change significantly. The ESR spectra show that, at low temperatures, the charge carriers are captured at the localized states. The bulk ferromagnetism is not observed at temperatures as low as 3.2 K. Magnetic properties are strongly temperature dependent and are not limited by the paramagnetism of free charge carriers. The temperature dependence of the ESR resonance field indicates the influence of ferromagnetic inclusions. The ferromagnetic shift of the resonance fields is observed up to a temperature of 80 K. The temperature dependence of the conductance reveals an exponential growth with the activation energy close to those obtained from the ESR measurements. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The on‐shell self‐energy of the uniform electron gas in its weak‐correlation limit
Authors: Ziesche P.
Published: March 2007

The ring‐diagram partial summation or random‐phase approximation (RPA) for the ground‐state energy of the uniform electron gas (with the density parameter rs) in its weak‐correlation limit rs → 0 is revisited. It is studied, which treatment of the self‐energy Σ (k, ω is in agreement with the Hugenholtz–van Hove (Luttinger–Ward) theorem μ – μ0 = Σ (kF, μ and which is not. As known from Macke (1950), Gell‐Mann/Brueckner (1957), Onsager/Mittag/Stephen (1966) and using the Seitz theorem (1940), the correlation part of the lhs has the RPA asymptotics rs + a ′ + O (rs) [in atomic units]. The use of renormalized RPA diagrams for the rhs yields the similar expression a ln rs + a ″ + O (rs with the sum rule a ′ = a ″ resulting from three sum rules for the components of a ′ and a ″. This includes in the second order of exchange the relation μ2x = Σ2x(kF, $ k^2_{\rm F}/2 $ [P. Ziesche, Ann. Phys. (Leipzig) 16(1), 45 (2007)]. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin lifetime from the Hanle effect and fine structure of excitonic levels in InAlAs/AlGaAs quantum dots
Authors: Sahli A. , Melliti A. , Maaref M. A. , Testelin C. , Lemaitre A. , Kuszelewicz R. , Voisin P.
Published: March 2007

Excitation of electron–hole pairs by circularly polarized light yields an electron spin polarization in InAlAs self‐assembled quantum dots. This spin polarization causes circular polarization of the photoluminescence light, its degree decreasing in a magnetic field perpendicular to the initial spin vector of the electron–hole pair (Hanle effect). The scaled spin lifetime $ g^{\rm e} _\bot $Ts, where $ g^{\rm e} _\bot $ is the transverse electron Landé factor and Ts is the electron spin lifetime is deduced from the Hanle curves and is of the order of 100 ps. It is attributed to the polarized spin confined in quantum dots. With increasing energy detection the width of the Hanle curve is reduced. The corresponding scaled electron–hole spin lifetime increases with increasing energy detection. We have also performed photoluminescence study of excitons localized in InAlAs quantum dots, in a longitudinal magnetic field. The magnetic‐field dependence of the linear and circular polarization evidences the exciton fine structure and helps to determine the anisotropic part of the exciton exchange, which is of the order of 14 μeV. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Isostructural BaSi2, BaGe2 and SrGe2: electronic and optical properties
Authors: Migas D. B. , Shaposhnikov V. L. , Borisenko V. E.
Published: March 2007

We have performed a theoretical study of the electronic band structure, density of states, dielectric function and absorption coefficient of isostructural BaSi2, BaGe2 and SrGe2 compounds by means of different ab initio methods. All materials are found to be indirect band‐gap semiconductors displaying almost equal dispersion of bands close to the gap region. The energy gaps of 0.83, 0.57 and 0.44 eV are estimated for BaSi2, BaGe2 and SrGe2, respectively. Analysis of the absorption coefficient of BaSi2 in comparison with data for other semiconducting silicides indicates its prospects for a solar cell application. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Deposition and properties of CdTe nanowires prepared by template replication
Authors: Enculescu Ionut , Sima Marian , Enculescu Monica , Enache Mihaela , Ion Lucian , Antohe Stefan , Neumann Reinhard
Published: March 2007

We used the template method to prepare CdTe wires with diameters ranging from 80 nm to 1 μm. As templates we used polycarbonate and polyethilene terephtalate ion track membranes and as the method of filling the pores of such membranes we employed electrochemical deposition. The conditions (i.e. bath composition and deposition potential) necessary to obtain the stoichiometric composition of the semiconductor were found. Scanning and transmission electron microscopy were employed for morphological characterization of the nano and microwires. Energy dispersive X‐ray analysis was employed for determining the Cd/Te ratio. Selected area electron diffraction was employed for structural measurements. Reflection spectroscopy measurements were performed on nanowire arrays for determining the band gap of the deposited nanostructures. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dephasing of free carriers and excitons in bulk CdTe
Authors: Sprinzl D. , Kunc J. , Ostatnický T. , Horodyský P. , Grill R. , Franc J. , Malý P. , Němec P.
Published: March 2007

In this paper we report on the measurements of the dephasing of free carriers and excitons using a self‐diffraction technique in thin platelets of CdTe with different concentration of preparation‐induced dislocations. We show that in a high‐quality sample at low temperature the characteristic dephasing time constant is 1 ps and 2 ps for free carriers and excitons, respectively. The increased concentration of preparation‐induced dislocations leads to much stronger acceleration of the dephasing for free carriers than for excitons. We also discuss the intensity and temperature dependence of the dephasing. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Study on defect states using deep level transient spectroscopy of ZnO grown by pulsed laser deposition
Authors: Kim Jae‐Hoon , Kim Eun Kyu
Published: March 2007

The pulsed laser deposition (PLD) was used for fabrication of ZnO films on a sapphire substrate. We modulated the parameters, temperature and gas pressure, for the growth condition. After the growth, X‐ray diffraction, photoluminescence (PL), and deep level transient spectroscopy (DLTS) measurements were performed. We had got PL spectra of high intensity from the ZnO film grown at low temperature. And the existence of the defect states was fewer, according to the result. But the crystalline quality was good for the film grown at high temperature. It seems to be that the relation between crystallization and defined electronic bandgap is weak. The DLTS measurements show some defects, but the signal is noisy. A Schottky contact by using Ti/Au and a high conductance seem to be the cause. We had simulated the DLTS spectra from assumed defects and matched to measurement results. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Microwave plasma synthesis of nano‐crystalline YSZ
Authors: Brossmann U. , Sagmeister M. , Pölt P. , Kothleitner G. , Letofsky‐Papst I. , Szabó D. V. , Würschum R.
Published: March 2007

Nanocrystalline yttria‐stabilized zirconia (YSZ) powder and compacts have been successfully synthesized by microwave plasma synthesis co‐evaporating Y and Zr precursors from a single source. Both liquid and solid mixtures of chemically homologous precursors were tested. Electron micrographs and X‐ray diffraction studies reveal small crystallites in the range 3–4 nm with a narrow size distribution. Crystallite sizes smaller than 25 nm are preserved even after subsequent annealing at temperatures up to 950 °C. A comparison with other gas‐phase synthesis routes of nanocrystalline YSZ is given. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A global Eta model on quasi‐uniform grids
Authors: Zhang Hai , Rančić Miodrag
Published: March 2007

The application of quasi‐uniform grids in global models of the atmosphere is an attempt to increase the computational efficiency by a more cost‐effective exploitation of the computing infrastructure. This paper describes the development of a global version of NCEP's regional, step‐coordinate, Eta model on two quasi‐uniform grids: cubic and octagonal. The governing equations are expressed in a general curvilinear form, so that the cubic and the octagonal versions of the model share the same code in spite of different mapping of the computational domain.

The dynamical core of the derived global Eta model is successfully tested in the benchmark test of Held and Suarez. The model with the step‐wise formulation of the terrain and full physics is integrated in a series of tests with real data, and the results are compared both with the analysis and the results of the regional Eta model. Copyright © 2007 Royal Meteorological Society
Impact of the Indian Ocean on ENSO variability in a hybrid coupled model
Authors: Yeh Sang‐Wook , Wu Renguang , Kirtman Ben P.
Published: March 2007

This study examines the impact of the Indian Ocean on El Niño and the Southern Oscillation (ENSO) variability through a series of numerical experiments with a hybrid coupled model. In the control run, an atmospheric general circulation model (AGCM) is coupled to the Zebiak–Cane simple ocean model in the tropical Pacific. Outside the tropical Pacific climatological sea surface temperatures are prescribed in the control simulation. In the first experiment, sea surface temperature anomalies (SSTAs) in the Indian Ocean are statistically predicted based on the state of the Pacific, and used to force the atmosphere. In the second experiment, a slab thermodynamic mixed layer model is coupled to the AGCM in the Indian Ocean. The Indian Ocean modifies the ENSO frequency via interactions with the Indian monsoon, but only when air–sea interactions in the Indian Ocean are included in the experimental design (i.e. the second experiment). The inclusion of the Indian Ocean, however, has little impact on the ENSO amplitude, which is at variance with other coupled simulations, suggesting that some missing dynamics or physics (i.e. Indian Ocean dynamics, Indonesian Throughflow, etc.) may play an important role. The Indian summer monsoon is more tightly coupled to ENSO in the second experiment than in the control run and the first experiment. The power spectrum of the Indian monsoon rainfall has a significant biennial time‐scale of around 20–30 months in the second experiment, which may enhance the biennial time‐scale of ENSO variability through a shift of the horizontal structure of zonal wind stress variability in the central equatorial Pacific. Copyright © 2007 Royal Meteorological Society
A modelling study of aerosol impacts on cloud microphysics and radiative properties
Authors: Cheng Chao‐Tzuen , Wang Wei‐Chyung , Chen Jen‐Ping
Published: March 2007

A warm cloud microphysical parameterization was incorporated into a regional model to study the sensitivity to aerosols of cloud‐radiative properties and precipitation. Assuming a trimodal lognormal aerosol size distribution, the aerosol numbers were explicitly calculated from prognostic aerosol masses, considering advection, diffusion, and cloud and raindrop activation/deactivation processes. Clean continental, average continental and urban aerosols, each with different modal parameters, were used to serve as condensation nuclei (CCN) of cloud‐ and raindrops, whose activations depended on supersaturation and aerosol composition.

Consistent with other studies, simulations conducted for a warm cloud system indicate that more aerosols result in more cloud water and more, but smaller, cloud drops, yielding increases in cloud albedo and decreases in surface precipitation. For example, the cloud drop effective radius decreased from ∼9 µm for clean continental aerosols to ∼5 and ∼2 µm, respectively, for average continental and urban aerosols, resulting in an increase in the respective cloud water path by ∼10% and ∼35% and cloud albedo by ∼6% and ∼12%. On the other hand, the accumulated precipitation decreased from 2.2 mm for clean continental aerosols to 1.9 and 1.2 mm, respectively, for average continental and urban aerosols. The presence of giant nuclei increased both the cloud drop effective radius and the precipitation, while the use of volumetric cloud drop radius tended to result in larger estimated cloud solar radiative forcing than the use of effective cloud drop radius. Copyright © 2007 Royal Meteorological Society
Towards a new hybrid cumulus parametrization scheme for use in non‐hydrostatic weather prediction models
Authors: Kuell V. , Gassmann A. , Bott A.
Published: March 2007

Classical mass flux parametrization schemes for cumulus convection generally transport heat and moisture only but do not include a net mass transport. This is well justified for large grid spacings comprising the whole convective circulation in the local grid column, such that all convective mass fluxes locally cancel out. A conceptual problem arises for finer grid spacings as used in contemporary numerical weather prediction (NWP) models, when convection becomes partially resolvable. This problem can be overcome by the hybrid approach presented here. Only updraft and downdraft are parametrized with a net mass transport; the environmental subsidence is treated by the grid‐scale equations. The total mass flux in the continuity equation is split into a grid‐scale and a subgrid‐scale contribution. This parametrization scheme is designed for use in any nonlinear, non‐hydrostatic and fully compressible NWP model. We here have chosen the Lokal–Modell (LM) of Deutscher Wetterdienst.

Idealized dry mass lifting experiments (without convective heat transport) demonstrate the feasibility of the hybrid approach. Entrainment causes grid‐scale convergence and the detrained air, if set to the environmental temperature, spreads mainly horizontally on the grid. Gravity waves are generated when convection starts and ends. Whereas their amplitude depends on the details of the switching on and off of convection, the stationary state (after about 30 minutes) does not. Four model runs with different grid spacings (3.5 km to 28 km) confirm that the mass exchange between the model grid and the parametrization scheme is independent of the chosen grid spacing. Total mass in a convective circulation cell is conserved to better than 0.1%, but only if the damping layer at the upper boundary of the LM is shifted to above 20 km.

For moist convection (with convective heat transport), a simple cloud model for an updraft has been set up. As the detrained air at the cloud top is colder than the environment, it moves down by about 1 km but then mainly spreads horizontally again over several tens of kilometres as in the dry case without convective heat transport.

The hybrid mass flux approach with both a grid‐scale and a subgrid‐scale contribution may fill the gap between coarse‐grid models (grid spacing > 50 km) with classical parametrization schemes, and very highly resolved explicit convection modelling (with a grid spacing of the order of 100 m). Copyright © 2007 Royal Meteorological Society
Boundary layer mechanisms in extratropical cyclones
Authors: Beare Robert J.
Published: March 2007

This paper revisits the mechanism for the interaction of the boundary layer with extratropical cyclones. Two diagnostic approaches are compared: Ekman pumping and potential vorticity. Ekman pumping derives from the boundary layer stress which induces convergence and ascent. boundary layer potential vorticity contains in a single quantity both the vorticity and stratification. These quantities are compared for an idealized extratropical cyclone life cycle simulated with the Met Office Unified Model.

A significant component of the boundary layer stress and thus Ekman pumping at occlusion is forced by the cold conveyor‐belt jet in the unstable boundary layer. In contrast, much of the boundary layer depth‐averaged potential vorticity is contained within the stable warm‐sector region. Inversion of the warm‐sector PV indicates a small local deepening of about 2.5 hPa. Moreover, switching off the boundary layer mixing in the unstable cold sector has much more impact than in the stable warm sector.

The sensitivity of the cyclone and its boundary layer to basic‐state jet strength is then investigated. The maximum friction velocity scales closely with the initial maximum jet strength. This demonstrates the important role of the large‐scale flow in organizing the boundary layer structure. Changes in the minimum pressure produced by altering the boundary layer parametrization correspond closely to changes in the surface stress averaged over the cyclone. Different operational changes to the boundary layer scheme produce small and compensating changes to the cyclone minimum pressure over three days. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd
The Met Office global four‐dimensional variational data assimilation scheme
Authors: Rawlins F. , Ballard S. P. , Bovis K. J. , Clayton A. M. , Li D. , Inverarity G. W. , Lorenc A. C. , Payne T. J.
Published: March 2007

The Met Office has developed a 4D‐Var data assimilation system, which was implemented in the global forecast system on 5 October 2004. This followed a development path based on the previous 3D‐Var configuration, with many aspects kept in common. A 4D‐Var capability was provided by the introduction of a linear perturbation forecast model based on the Unified Model, the non‐hydrostatic grid‐point model producing our operational forecasts.

There were clear advantages in verification of forecasts compared to the equivalent 3D‐Var configuration, with an improvement of 2.6% in a composite skill score verified against observations during pre‐operational trials. The largest differences in model evolution occur in storm‐track regions in the extratropics. Overall, improvements in verification scores as measured against observations were larger than those measured against analyses, particularly at upper levels. There is an improvement in verification of surface parameters (10 m wind, 1.5 m temperature and relative humidity) against analyses. The strongest impact on fitting observations is seen for satellite radiances with weighting functions peaking in the stratosphere and upper troposphere. The largest changes to assimilation increments occurred in the top model levels, particularly wind increments which became much larger near the model top.

Similarities were found in the signal of 4D‐Var versus 3D‐Var for models at two different resolutions, from which we infer that low‐resolution trials remain valid for exploring some aspects of 4D‐Var before confirmation in full‐scale tests. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd
Role of the quasi‐biweekly oscillation in the onset of convection over the Indochina Peninsula
Authors: Wen Min , Zhang Renhe
Published: March 2007

The characteristics of convection onset over the Indochina Peninsula and its possible mechanism are investigated using the reanalysis of the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) and the black‐body temperature at the top of the cloud (TBB). Results show that the convection onset occurs before the systemic northward progression of the tropical convection and is earlier than the onset of the summer monsoon over this region. The prominent difference between the onset of convection and that of the summer monsoon appears in the westmost part of the western Pacific subtropical high. When the convection bursts, the Indochina Peninsula is under the control of the western Pacific subtropical high. However, the summer monsoon onset follows the splitting of the subtropical high belt and the eastward retreat of the western Pacific subtropical high out of the Indochina Peninsula.

The climatological features of TBB over the Indochina Peninsula indicate that the convective activities have a close relationship with the quasi‐biweekly oscillation (QBWO). Based on the onset dates determined by the TBB data, case‐studies and composite analyses are implemented on exploring the possible mechanism of the convection onset. It is found that the onset of convection is mainly influenced by factors as follows. The wet phase of QBWO of the tropical convection propagates northward from Sumatra to the Indochina Peninsula. Over the southern Indochina Peninsula, anomalous southerlies (the Rossby wave response to the tropical convective QBWO) are beneficial to both the northward progression of the convective disturbances and the convergence of the low‐level moisture flux. Furthermore, the Indochina Peninsula is easily affected by any cold surge invading southwards from higher latitudes, which intensifies the convective activities when merging with the wet/warm current. Copyright © 2007 Royal Meteorological Society
‘N‐in‐one’ strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan
Authors: Li Austin C. , Gohdes Mark A. , Shou Wilson Z.
Published: March 2007

This paper describes a new strategy that utilizes the fast trap mode scan of the hybrid triple quadrupole linear ion trap (QqQLIT) for the identification of drug metabolites. The strategy uses information‐dependent acquisition (IDA) where the enhanced mass scan (EMS), the trap mode full scan, was used as the survey scan to trigger multiple dependent enhanced product ion scans (EPI), the trap mode product ion scans. The single data file collected with this approach not only includes full scan data (the survey), but also product ion spectra rich in structural information. By extracting characteristic product ions from the dependent EPI chromatograms, we can provide nearly complete information for in vitro metabolites that otherwise would have to be obtained by multiple precursor ion scan (prec) and constant neutral loss (NL) analysis. This approach effectively overcomes the disadvantages of traditional prec and NL scans, namely the slow quadrupole scan speed, and possible mass shift. Using nefazodone (NEF) as the model compound, we demonstrated the effectiveness of this strategy by identifying 22 phase I metabolites in a single liquid chromatography/tandem mass spectrometry (LC/MS/MS) run. In addition to the metabolites reported previously in the literature, seven new metabolites were identified and their chemical structures are proposed. The oxidative dechlorination biotransformation was also discovered which was not reported in previous literature for NEF. The strategy was further evaluated and worked well for the fast discovery setting when a ballistic gradient elution was used, as well as for a simulated in vivo setting when the incubated sample (phase I metabolites) was spiked to control human plasma extract and control human urine. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of hydrogen, carbon and oxygen isotope ratios of ethanol in aqueous solution at millimole levels
Authors: Yamada Keita , Yoshida Naohiro , Calderone Giovanni , Guillou Claude
Published: March 2007

Three stable isotope ratios, D/H, 13C/12C and 18O/16O, are measurable in ethanol, an important organic compound that is used as a material for food and beverages, fuel and chemical feedstock, and as a substance related to metabolism. We developed a simple and rapid method of measurement of three isotope ratios of ethanol in aqueous solution at millimole levels using gas chromatography‐high‐temperature conversion or combustion‐isotope ratio mass spectrometry (GC‐TC/C‐IRMS) combined with solid‐phase microextraction (SPME). Using this method, the δ value for ethanol was determined in 30 min for δD and δ13C, and in 75 min for δ18O with precisions of ±9‰, ±0.3‰ and ±0.7‰, respectively, for δD, δ13C, and δ18O. An advantage of this process is that it requires no distillation for ethanol purification. The method is useful for small quantities of analyte with low ethanol concentrations, which is expected for environmental and metabolic studies. Copyright © 2007 John Wiley & Sons, Ltd.
Detection and sequence determination of a new variant β‐lactoglobulin II from donkey
Authors: Cunsolo Vincenzo , Costa Alessia , Saletti Rosaria , Muccilli Vera , Foti Salvatore
Published: March 2007

The sequence determination of a new variant of β‐LG II, detected as a minor component by reversed‐phase high‐performance liquid chromatography/electrospray ionization mass spectrometry (RP‐HPLC/ESI‐MS) analysis of the whey fraction from a milk sample taken from an individual donkey belonging to the ‘Ragusana’ species of eastern Sicily, is reported. Direct RP‐HPLC/ESI‐MS analysis of the whey fraction from this milk sample allowed the identification of a new variant of β‐LG II, based on the determination of the Mr of the intact protein. The new protein, with an experimentally determined Mr of 18311 Da, was detected as a minor component in the whey fraction investigated. Matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF)MS and RP‐HPLC/ESI‐MS/MS analyses of the tryptic digest of the new protein demonstrate that it presents two amino acid substitutions with respect to the sequence of β‐LG II A, namely a substitution Pro→Cys at position 110, and a substitution Asp→Gly at position 162. The disulfide bonds between the four cysteines, not directly determined in donkey's and horse's β‐LG II, were shown to occur between Cys106‐Cys120 and Cys66‐Cys161, as in other mammalian β‐LGs. The new β‐LG II variant from donkey was named D. Copyright © 2007 John Wiley & Sons, Ltd.
Iowa radon leukaemia study: a hierarchical population risk model for spatially correlated exposure measured with error
Authors: Smith Brian J. , Zhang Lixun , Field R. William
Published: March 2007

This paper presents a Bayesian model that allows for the joint prediction of county‐average radon levels and estimation of the associated leukaemia risk. The methods are motivated by radon data from an epidemiologic study of residential radon in Iowa that include 2726 outdoor and indoor measurements. Prediction of county‐average radon is based on a geostatistical model for the radon data which assumes an underlying continuous spatial process. In the radon model, we account for uncertainties due to incomplete spatial coverage, spatial variability, characteristic differences between homes, and detector measurement error. The predicted radon averages are, in turn, included as a covariate in Poisson models for incident cases of acute lymphocytic (ALL), acute myelogenous (AML),
chronic lymphocytic (CLL), and chronic myelogenous (CML) leukaemias reported to the Iowa cancer registry from 1973 to 2002. Since radon and leukaemia risk are modelled simultaneously in our approach, the resulting risk estimates accurately reflect uncertainties in the predicted radon exposure covariate. Posterior mean (95 per cent Bayesian credible interval) estimates of the relative risk associated with a 1 pCi/L increase in radon for ALL, AML, CLL, and CML are 0.91 (0.78–1.03), 1.01 (0.92–1.12), 1.06 (0.96–1.16), and 1.12 (0.98–1.27), respectively. Copyright © 2007 John Wiley & Sons, Ltd.
The relevance of situation awareness in older adults’ cognitive functioning: a review
Authors: Caserta Ryan J. , Abrams Lise
Published: March 2007

Age-related declines in cognition may have detrimental effects on older adults’ ability to complete everyday activities that young- and middle-aged individuals perform automatically. Theories of cognitive aging have found deficits in older adults’ fluid intelligence, capacity for inhibition, number of processing resources, and speed of processing, and in recent years, studies have proposed cognitive strategies to ameliorate these declines. However, few strategies directly train the cognitive strategies necessary to improve performance in dynamic environments and physical activities. One such strategy may be the enhancement of situation awareness, the capability to perceive and understand one’s environment. Although the term has typically been applied to pilots and other expert performers, situation awareness may also be relevant to cognitive aging, where older adults’ perception and comprehension of their environment become critical to everyday functioning and physical activities. If older adults’ situation awareness can be facilitated, then it may be possible to reduce the impact of age-related cognitive declines, allowing older adults to successfully participate in dynamic situations and sports where the environment is constantly changing (e.g., driving and tennis). The following review outlines cognitive deficits in aging, details their relation to situation awareness, and discusses how training in situation awareness may reduce cognitive declines.
Astonishing diversity of natural surfactants: 2. Polyether glycosidic ionophores and macrocyclic glycosides
Authors: Dembitsky Valery M.
Published: March 2007

Polyether glycosidic ionophores and macrocyclic glycosides are of great interest, especially for the medicinal and pharmaceutical industries. These biologically active natural surfactants are good prospects for the future chemical preparation of compounds useful as antibiotics, anticancer agents, or in industry. More than 300 interesting and unusual natural surfactants are described in this review article, including their chemical structures and biological activities.
Tissue‐dependent alterations in lipid mass in mice lacking glycerol kinase
Authors: Golovko Mikhail Y. , Hovda Johnathan T. , Cai Zong‐Jin , Craigen William J. , Murphy Eric J.
Published: March 2007

Glycerol kinase (ATP:glycerol‐3‐phosphotransferase, EC 2.7.1.30, glycerokinase) (Gyk) has a central role in plasma glycerol extraction and utilization by tissues for lipid biosynthesis. Gyk deficiency causes various phenotypic changes ranging from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth and psychomotor retardation. To better understand the potential role of Gyk in tissue lipid metabolism, we determined phospholipid (PL), cholesterol (Chol), and triacylglycerol (TG) mass in a number of tissues from mice lacking Gyk. We report a tissue‐dependent response to Gyk gene deletion. Tissues with elevated total PL mass (brain, kidney, muscle) were characterized by the increased mass of ethanolamine glycerophospholipids (EtnGpl), choline glycerophospholipids, and phosphatidylserine (PtdSer). In heart, lipid changes were characterized by a reduction in total PL, including decreased EtnGpl, phosphatidylinositol, and PtdSer mass and decreased TG and FFA mass. In parallel with tissue PL alterations, tissue Chol was also changed, maintaining a normal Chol/PL ratio. Under conditions of Gyk deficiency, we speculate that glycerol‐3‐phosphate and lipid production is maintained via alternative biosynthesis, including glycolysis, glyceroneogenesis, or by direct acylation of glycerol in brain, muscle, kidney, and liver, but not in heart.
Vaccenic acid metabolism in the liver of rat and bovine
Authors: Gruffat Dominique , De La Torre Anne , Chardigny Jean‐Michel , Durand Denys , Loreau Olivier , Bauchart Dominique
Published: March 2007

Hepatic metabolism of vaccenic acid (VA), especially its conversion into CLA, was studied in the bovine (ruminant species that synthesizes CLA) and in the rat (model for nonruminant) by using the in vitro technique of liver explants. Liver tissue samples were collected from fed animals (5 male Wistar rats and 5 Charolais steers) and incubated at 37°C for 17 h under an atmosphere of 95% O2/5% CO2 in medium supplemented with 0.75 mM of FA mixture and with 55 μM [1‐14C]VA. VA uptake was about sixfold lower in bovine than in rat liver slices (P<0.01). For both species, VA that was oxidized to partial oxidation products represented about 20% of VA incorporated by cells. The chemical structure of VA was not modified in bovine liver cells, whereas in rat liver cells, 3.2% of VA was converted into 16∶0 and only 0.33% into CLA. The extent of esterification of VA was similar for both animal species (70–80% of incorporated VA). Secretion of VA as part of VLDL particles was very low and similar in rat and bovine liver (around 0.07% of incorporated VA). In conclusion, characteristics of the hepatic metabolism of VA were similar for rat and bovine animals, the liver not being involved in tissue VA conversion into CLA in spite of its high capacity for FA desaturation especially in the rat. This indicates that endogenous synthesis of CLA should take place exclusively in peripheral tissues.