bluuebunny/crossref_metadata_2025 huggingface dataset:
Klinische Validität der K-CAB bei Kindern mit ADHS
Authors: Toussaint Anne , Petermann Franz
Published: August 2010

Die Studie diente der klinischen Validierung der computerbasierten Testbatterie K-CAB bei Kindern mit ADHS. Die dem Verfahren zugrunde liegende PASS-Theorie (Planungsfähigkeit, Aufmerksamkeit, simultane und sequenzielle Verarbeitung) sollte auf ihren Informationsgewinn bezüglich der Diagnostik von ADHS überprüft werden. Die K-CAB-Testprofile von 28 deutschen Kindern mit ADHS-Symptomatik im Alter zwischen 6;5 und 11;0 Jahren wurden mit den Profilen einer nach Alter und Geschlecht parallelisierten Kontrollgruppe verglichen. Die Ergebnisse zeigten, dass die ADHS-Kinder zwar signifikant schlechter auf der Aufmerksamkeits-Skala der K-CAB abschnitten, in den Bereichen Planungsfähigkeit, Simultane und Sequenzielle Verarbeitung jedoch durchschnittlich gute Ergebnisse erzielten. In dreien von vier Aufmerksamkeitsparametern schnitten die ADHS-Kinder signifikant schlechter ab. Sie machten mehr Auslassungsfehler und reagierten insgesamt variabler und langsamer als die Kontrollgruppe. Die Untersuchung der diskriminanten Validität der Testbatterie zeigte, dass durch den Untertest Aufmerksamkeit 80.4 % der Kinder beider Gruppen richtig klassifiziert werden konnten. Schlussfolgernd kann festgestellt werden, dass eine neuropsychologische Testbatterie wie die K-CAB zwar wichtige Hinweise auf das individuelle Leitungsprofil geben kann, eine diagnostische Klassifikation aber nicht alleine auf den Testergebnissen basieren kann.
Biofeedbacktherapie eines traumatisierten Migranten mit chronischen Schmerzen
Authors: Morina  , Müller
Published: August 2010

Wir berichten von einem 40-jährigen kurdischen Patienten, der sechs Jahr lang aus politischen Gründen inhaftiert war. Der Patient leidet an einer posttraumatischen Belastungsstörung und komorbiden chronischen Schmerzen. Zur Schmerzbewältigung wurde der Patient mittels Biofeedback initial verhaltenstherapeutisch behandelt. Die Intervention zeigte gute Effekte auf die Schmerzen. Anamnese, Diagnostik, Therapieplan sowie Therapieverlauf werden beschrieben.
Importance of auroral features in the search for substorm onset processes
Authors: Akasofu Syun‐Ichi , Lui A. T. Y. , Meng C.‐I.
Published: August 2010

Auroral features at about the onset time of substorms are revisited to emphasize their importance in considering substorm onset processes. This study is based on all‐sky camera photographs and meridian scanning photometer records from a single station. First, in considering substorm onset processes, it is crucial to pay attention to the implication of the fact that an auroral arc located just poleward side of the initially brightening arc becomes active only after, not before, onset. Second, prior to substorm onset, there occurs a rapid equatorward shift, or more like narrowing the width, of the equatorward half of the oval, not the whole oval, without any distinct and immediate changes of the interplanetary magnetic field (IMF) Bz component, except that the shift tends to occur after the southward turning of the IMF. These phenomena suggest that some processes take place spontaneously at a distance of less than 10 RE, perhaps near the boundary between the central plasma sheet and the boundary plasma sheet, after the magnetosphere is primed by the IMF southward turning. Thus, it is concluded that substorm models in the near−Earth initiation category satisfy the observational constraints provided by the present paper. Because of our limited data set in terms of observations at single stations, new ground‐based observations are suggested to confirm our results.
Dynamics of advection‐driven upwelling over a shelf break submarine canyon
Authors: Allen S. E. , Hickey B. M.
Published: August 2010

The response over a submarine canyon to a several day upwelling event can be separated into three phases: an initial transient response; a later, much longer, “steady” advection‐driven response; and a final relaxation phase. For the advection‐driven phase over realistically steep, deep, and narrow canyons with near‐uniform flow and stratification at rim depth, we have derived scale estimates for four key quantities. Observations from 5 real‐world canyon studies and 3 laboratory studies are used to validate the scaling and estimate the scalar constant for each scale. Based on 4 geometric parameters of the canyon, the background stratification, the Coriolis parameter, and the incoming current, we can estimate (1) the depth of upwelling in the canyon to within 15 m, (2) the deep vorticity to within 15%, and (3) the presence/absence of a rim depth eddy can be determined. Based on laboratory data, (4) the total upwelling flux can also be estimated. The scaling analysis shows the importance of a Rossby number based on the radius of curvature of isobaths at the upstream mouth of the canyon. This Rossby number determines the ability of the flow to cross the canyon isobaths and generate the pressure gradient that drives upwelling in the canyon. Other important scales are a Rossby number based on the length of the canyon which measures the ability of the flow to lift isopycnals and a Burger number based on the width of the canyon that determines the likelihood of an eddy at rim depth. Generally, long canyons with sharply turning upstream isobaths, strong incoming flow, small Coriolis parameter, and weak stratification have the strongest upwelling response.
Modeling the Mediterranean Sea interannual variability during 1961–2000: Focus on the Eastern Mediterranean Transient
Authors: Beuvier J. , Sevault F. , Herrmann M. , Kontoyiannis H. , Ludwig W. , Rixen M. , Stanev E. , Béranger K. , Somot S.
Published: August 2010

This work is dedicated to the study of the climate variability of the Mediterranean Sea, in particular the study of the Eastern Mediterranean Transient (EMT) which occurred in the early 1990s. Simulations of the 1961–2000 period have been carried out with an eddy‐permitting Ocean General Circulation Model of the Mediterranean Sea, driven by realistic interannual high‐resolution air‐sea fluxes. Using different databases for the river runoff, Black Sea inflow, and Atlantic thermohaline characteristics at climatological or interannual scales, we assess the effects of the non‐atmospheric hydrological forcings on the simulation of the interannual variations of the Mediterranean circulation. The evolution of the basin‐scale heat content is in very good agreement with the observations (especially in the surface and intermediate layers), while the agreement is lower for the evolution of the salt content. Convection events in the Aegean Sea are noticed in the simulations between 1972 and 1976, in the late 1980s, and around the EMT period. The formation rates of Cretan Deep Water (CDW) are different during these periods, allowing or preventing the spreading of CDW into the eastern Mediterranean. The sequence of the EMT events is well reproduced: the high winter oceanic surface cooling and net evaporation over the Aegean Sea in the early 1990s, the high amount of dense CDW formed during these winters, and then the overflow and the spreading of this CDW in the eastern Mediterranean. Among the preconditioning processes suggested in the literature, we find that changes in the Levantine surface circulation, possibly induced by the presence in the Cretan Passage of anticyclonic eddies and a lasting period with reduced net precipitation over the eastern Mediterranean, lead to an increase of the salt content of the Aegean Sea. Changes in the Black Sea freshwater inflow or in the characteristic of the Atlantic Water entering at the Gibraltar Strait also modify the thermohaline state of the Aegean Sea before the EMT. But, as none of these preconditioning factors has a lasting impact on lowering the vertical stratification of the Aegean Sea, we conclude that concerning the EMT, the major triggering elements are the atmospheric fluxes and winds occurring in winters 1991–1992 and 1992–1993.
Modeling iceberg‐rafted sedimentation in high‐latitude fjord environments
Authors: Mugford R. I. , Dowdeswell J. A.
Published: August 2010

An iceberg model, SedBerg, has been developed to simulate sedimentation in high‐latitude glaciated fjords. Sediments deposited in fjords provide an important record of glaciological response to changing climatic conditions. The model simulates the formation, drift, and melt of a population of icebergs utilizing Monte Carlo–based techniques with a number of underlying parametric probability distributions to describe the stochastic behavior of iceberg formation and dynamics. The model captures iceberg dynamics and melt in fjord environments and has been applied to Kangerdlugssuaq Fjord in east Greenland as an example of an iceberg‐dominated sedimentary environment. Sedimentation has been simulated over the past 1500 years, encompassing the climatic intervals of the Medieval Warm Period (MWP) and the Little Ice Age (LIA). Model results have been compared with the observed sedimentary record. The model demonstrates that the glaciological regime, e.g., basal debris thickness, mean annual calving rate, mean iceberg size, plays a more important role than the direct influence of climate (ocean and air temperatures) on iceberg sedimentation rate, although often changes in climate result in changes to the glaciological regime.
Effect of nonlocal transverse mixing on river flows dispersion: A numerical study
Authors: Pannone Marilena
Published: August 2010

A series of Lagrangian numerical simulations is performed to examine the dispersion process in open channel flows and to explain through a simple conceptual model its systematic deviations from the ideal long‐term one‐dimensional regime even in the case of straight axis and fixed impervious bed. The starting point is represented by a suitably depth‐averaged transport equation, with generally nonlocal turbulent mixing, solved in terms of particles trajectories and their first‐ and second‐order moments. Input data refer to six rivers of southern Italy, for which the irregular section morphology is known from a field survey. As the governing equation predicts, and according to experimental observations, in the case of variable cross‐sectional diffusion the tracer cloud exhibits a permanent and asymmetric peripheral drift toward the shallow boundary zones, with a remarkable deceleration along the main flow direction. Longitudinal inertia moments tend to become linear after a period equal to twice the single river diffusive time and sometimes show an early anomalous change of slope. Transverse inertia moments experience an initial very fast increment as compared to the theoretical value corresponding to the uniform transverse concentration and, after a peak, tend to stabilize about a smaller constant. Centrifugal moments remain, in any case, relatively limited, indicating that longitudinal and transverse axes practically identify with the plume principal directions, no matter how irregular and asymmetric the river section is.
Climate Science in a Postmodern World
Authors: Verosub Kenneth L.
Published: August 2010

Like many readers of Eos, I have found it hard to understand the persistence of climate doubters and climate skeptics. How can they not accept the science? An important clue can be found in an editorial by Daniel Henninger in the Wall Street Journal that made a connection between climate science and postmodernism [Henninger, 2009]. Postmodernism is a concept that permeates the humanities and the social sciences. In its simplest terms, it postulates that truth is a relative concept. Facts exist, but their interpretation is determined as much by society, culture, politics, and economics as by scientific objectivity. From this perspective, any interpretation is as valid as any other. So, for instance, Herman Melville's Moby Dick can be seen as a novel equally about morality, homosexuality, the repression of the masses, the quest for God, or the killing of whales in the nineteenth century. All interpretations are valid, and all truth is relative.
AGU Committee Volunteers for 2010–2012
Authors: Anonymous
Published: August 2010

The success of AGU as a scientific society depends on dedicated volunteers who reflect the diverse interests of our international membership. To function effectively, we need a strong core of volunteers who generously devote time, talent, and energy to Union committee work. To our members who have stepped up and unselfishly volunteered to serve for 2010–2012, I say thank you for your commitment to AGU's mission and programs. It is through your leadership and example that we will achieve our goals as an organization.

The next 2 years promise to be an exciting time as we continue the transformation of AGU to better serve our members and society. We will build upon our traditional strengths as a scholarly organization while at the same time embarking on new initiatives to advance our science and its relevance to the modern world. Volunteers serving on AGU committees will play an essential role in moving us forward by providing policy guidance, program oversight, and innovative ideas for new ventures in keeping with our recently adopted strategic plan.
Constraints on shallow mantle viscosity from morphology and deformation of fast‐spreading ridges
Authors: Choi E. , Buck W. R.
Published: August 2010

We show that the morphology and the deformation of a fast spreading ridge constrain shallow upper mantle viscosity. A fast spreading center is simulated in a numerical model that couples tectonic deformation due to plate spreading and periodic dike emplacements. The amount of magma intruded into dikes or extruded is enough to make a 7 km thick crust and the axial lithosphere is fixed at ∼2 km thickness. For low viscosities (≤1019 Pa·s), the model spreading center is marked by an axial high with relief governed by the axial density structure. For high viscosities (≥1020 Pa·s) the axial morphology is a valley and extensional brittle deformation is distributed away from the near‐axis region. The observed morphology and deformation of fast spreading ridges are not consistent with the high mantle viscosity estimated for very dry olivine, as some suggest may result from partial melting related dehydration.
Interleukin 10 decreases MICA expression on melanoma cell surface
Authors: Serrano Antonio E , Menares‐Castillo Evelyn , Garrido‐Tapia Macarena , Ribeiro Carolina Hager , Hernández Carolina J , Mendoza‐Naranjo Ariadna , Gatica‐Andrades Marcela , Valenzuela‐Diaz Rodrigo , Zúñiga Roberto , López Mercedes N , Salazar‐Onfray Flavio , Aguillón Juan‐Carlos , Molina María‐Carmen
Published: August 2010

Natural‐killer group 2, member D (NKG2D) binds to a variety of ligands, including the major histocompatibility complex (MHC) class I chain‐related proteins (MIC) and UL16‐binding proteins (ULBP). It is regarded as a co‐activating receptor on NK cells, having an important role in the cell‐mediated immune response to tumours. We studied the influence of interleukin (IL)‐10 on the regulation of MIC and ULBP expression on melanoma cells, and its effect on the cytotoxic function of NK cells in vitro. Here, we show that, in the presence of IL‐10, FMS mel and BL mel cell lines decreased MICA and ULBP2 surface expression, whereas MHC class I did not change substantially on the cell surface. MICA mRNA levels decreased in IL‐10‐treated FMS and IL‐10‐transduced BL cell lines. Interestingly, we observed that MICB surface expression and its mRNA levels increased upon IL‐10 treatment in a melanoma cell line. These changes in NKG2D ligands surface expression patterns owing to IL‐10 treatment resulted in an effect on lysis susceptibility mediated by lymphocyte‐activated killer cells, as tumour cell lines that displayed a higher decrease of MICA on their surface had lower levels of lysis. In addition, expression of CD107a was downregulated on the surface of NK cells following stimulation with IL‐10‐treated FMS cells. Our results suggest a novel function for IL‐10 in the modulation of NKG2D ligand expression and in the control of cytotoxicity mediated by NKG2D/NKG2D ligand axis.
In-situ Fourier transform infra red spectroelectrochemistry as a probe of electrocatalysis
Authors: Christensen P. A.
Published: August 2010

The aim of this paper is to highlight recent advances in the understanding of electrocatalysis that have been achieved using in-situ electrochemical Fourier Transform Infra Red (FTIR) spectroscopy; in doing so, the paper seeks to describe the key principles of the application of the technique.
Disfluency Characteristics Observed in Young Children With Autism Spectrum Disorders: A Preliminary Report
Authors: Plexico Laura W. , Cleary Julie E. , McAlpine Ashlynn , Plumb Allison M.
Published: August 2010

This descriptive study evaluates the speech disfluencies of 8 verbal children between 3 and 5 years of age with autism spectrum disorders (ASD). Speech samples were collected for each child during standardized interactions. Percentage and types of disfluencies observed during speech samples are discussed. Although they did not have a clinical diagnosis of stuttering, all of the young children with ASD in this study produced disfluencies. In addition to stuttering-like disfluencies and other typical disfluencies, the children with ASD also produced atypical disfluencies, which usually are not observed in children with typically developing speech or developmental stuttering. (Yairi & Ambrose, 2005).
Influence of surface migration on the spatial resolution of pulsed laser atom probe tomography
Authors: Gault B. , Müller M. , La Fontaine A. , Moody M. P. , Shariq A. , Cerezo A. , Ringer S. P. , Smith G. D. W.
Published: August 2010

The impact of laser pulsing on the field evaporation process is investigated for Al and W by pulsed laser atom probe tomography. Quantitative analysis reveals the influence on the spatial resolution of the peak temperature reached by the specimen following light absorption from the laser pulse. It is concluded that surface migration processes induce significant degradation of the lateral resolution, changing by 100% and 20%, respectively, for Al and W when the specimen temperature is increased from 4% to 7% of the material’s melting point, while the in-depth resolution is shown to remain nearly constant for both materials.
Structural, electrical, and optical properties of atomic layer deposition Al-doped ZnO films
Authors: Banerjee Parag , Lee Won-Jae , Bae Ki-Ryeol , Lee Sang Bok , Rubloff Gary W.
Published: August 2010

Al-doped ZnO (AZO) films of ∼100 nm thickness with various Al doping were prepared at 150 °C by atomic layer deposition on quartz substrates. At low Al doping, the films were strongly textured along the [100] direction, while at higher Al doping the films remained amorphous. Atomic force microscopy results showed that Al–O cycles when inserted in a ZnO film, corresponding to a few atomic percent Al, could remarkably reduce the surface roughness of the films. Hall measurements revealed a maximum mobility of 17.7 cm2/V s. Film resistivity reached a minima of 4.4×10−3 Ω cm whereas the carrier concentration reached a maxima of 1.7×1020 cm−3, at 3 at. % Al. The band gap of AZO films varied from 3.23 eV for undoped ZnO films to 3.73 eV for AZO films with 24.6 at. % Al. Optical transmittance over 80% was obtained in the visible region. The detrimental impact of increased Al resulting in decreased conductivity due to doping past 3.0 at. % is evident in the x-ray diffraction data, as an abrupt increase in the optical band gap and as a deviation from the Burstein–Moss effect.
Corrected field enhancement factor for the floating sphere model of carbon nanotube emitter
Authors: Pogorelov Evgeny G. , Chang Yia-Chung , Zhbanov Alexander I. , Lee Yong-Gu
Published: August 2010

We have corrected the field enhancement factor for the “floating sphere at emitter-plane potential” model with the finite anode-cathode distance. If ρ is the radius of sphere, h is the distance from cathode to the center of sphere, and l is the distance from the center to the anode, then the field enhancement factor is given as the following expression βsph=(2+7η−η2)(λ2−2λ+2)/[2η(1−λ)(2−λ)], where η=ρ/h, λ=ρ/l. This expression demonstrates reasonable behavior for three limiting cases: if h→ρ, if l→∞, and if l→ρ. We have compared our factor βsph with the field enhancement factor βtube for the “hemisphere on a post” model and the factor βell for the “hemiellipsoid on plane” model. We have shown realization of the approximate evaluation βtube≈(βsph+βell)/2.
Electrical conductivities of aluminum, copper, and tungsten observed by an underwater explosion
Authors: Sasaki Toru , Nakajima Mitsuo , Kawamura Tohru , Horioka Kazuhiko
Published: August 2010

Conductivities of dense aluminum, copper, and tungsten are evaluated using exploding wire discharges in water. Evolutions of the radius and the electrical resistance of exploding wire are measured together with direct pyrometric estimation of the temperature. The conductivities are evaluated based on the measurements and their density dependence is compared with theoretical predictions at a fixed temperature. The results indicate that regardless of materials, the conductivity has a minimum around 3% of solid density at temperature of 5000 K.
Femtosecond laser pulse energy transfer induced by plasma grating due to filament interaction in air
Authors: Yang Xuan , Wu Jian , Tong Yuqi , Ding Liang’en , Xu Zhizhan , Zeng Heping
Published: August 2010

We experimentally demonstrate the formation of a thin plasma grating lasted for several tens of picosecond induced by the strong interaction between two noncollinear femtosecond filaments in air. A time-delayed second-harmonic pulse propagating along one of the incident filaments is coupled and nonlinearly diffracted by the thin plasma grating, leading to an energy transfer to the other noncollinearly crossed femtosecond filament. The dependences of the plasma grating on the intensity ratios and relative polarizations between the input pulses are investigated.
Local strain in tunneling transistors based on graphene nanoribbons
Authors: Lu Yang , Guo Jing
Published: August 2010

A band-to-band tunneling field-effect transistor (FET) can achieve a subthreshold slope steeper than 60 mV/dec at room temperature, but the on-current is low due to existence of the tunneling barrier. Graphene has a monolayer-thin body which is amenable to strain. By using self-consistent quantum transport simulations, we show that with local strain applied at the tunneling junction between the source and the channel in a graphene nanoribbon tunneling FET, the on-current can be significantly improved by over a factor of 10 with the same off-current, no matter at the ballistic limit or in the presence of inelastic phonon scattering.
Human papillomavirus vaccine introduction in Vietnam: formative research findings
Authors: Nghi Nguyen Quy , LaMontagne D. Scott , Bingham Allison , Rafiq Mirriam , Mai Le Thi Phuong , Lien Nguyen Thi Phuong , Khanh Nguyen Cong , Hong Duong Thi , Huyen Dang Thi Thanh , Tho Nguyen Thi Thi , Hien Nguyen Tran
Published: August 2010

Background: Formative research is a useful tool for designing new health interventions. This paper presents key findings from formative research conducted in Vietnam to guide human papillomavirus (HPV) vaccine introduction. Methods: We explored the sociocultural environment, health system capacity and the policy-making process using a combined quantitative and qualitative methodology. Data collection was done through literature review, in-depth interviews, focus group discussions, observation checklists and a structured questionnaire on knowledge, attitudes and practices. Populations of interest included 11- to 14-year-old girls, their parents, community leaders, teachers, health workers, health and education officials, and policy-makers at all levels. Results:Although HPV vaccines are new, we found high potential acceptance among parents and girls. HPV vaccine introduction was also favourably supported by health professionals if assurances for system preparedness, e.g. cold chain and human resources, were made. There were no significant barriers from the policy perspective that would prevent the introduction of a new vaccine. However, several concerns related to this new vaccine would need to be adequately addressed before implementation. Conclusion: Our findings provide options for potential vaccine delivery strategies, appropriate communication strategies and targeted advocacy strategies to introduce HPV vaccines in the Vietnamese context.
Quantitative phosphoproteomic analysis reveals cAMP/vasopressin-dependent signaling pathways in native renal thick ascending limb cells
Authors: Gunaratne Ruwan , Braucht Drew W. W. , Rinschen Markus M. , Chou Chung-Lin , Hoffert Jason D. , Pisitkun Trairak , Knepper Mark A.
Published: August 2010

Quantitative mass spectrometry was used to identify hormone-dependent signaling pathways in renal medullary thick ascending limb (mTAL) cells via phosphoproteomic analysis. Active transport of NaCl across the mTAL epithelium is accelerated by hormones that increase cAMP levels (vasopressin, glucagon, parathyroid hormone, and calcitonin). mTAL suspensions from rat kidneys were exposed (15 min) to a mixture of these four hormones. Tryptic phosphopeptides (immobilized metal affinity chromatography-enriched) were identified and quantified by mass spectrometry (LTQ-Orbitrap) using label-free methodology. We quantified a total of 654 phosphopeptides, of which 414 were quantified in three experimental pairs (hormone vs. vehicle). Of these phosphopeptides, 82% were statistically unchanged in abundance in response to the hormone mixture. In contrast, 48 phosphopeptides were significantly increased, whereas 28 were significantly decreased. The population of up-regulated phosphopeptides was highly enriched in basophilic kinase substrate motifs (AGC or calmodulin-sensitive kinase families), whereas the down-regulated sites were dominated by “proline-directed” motifs (cyclin-dependent or MAP kinase families). Bioinformatic classification uncovered overrepresentation of transmembrane transporters, protein phosphatase regulators, and cytoskeletal binding proteins among the regulated proteins. Immunoblotting with phospho-specific antibodies confirmed cAMP/vasopressin-dependent phosphorylation at Thr96, Ser126, and Ser874 of the Na
+
:K
+
:2Cl
−
cotransporter NKCC2, at Ser552 of the Na
+
:H
+
exchanger NHE3, and at Ser552 of β-catenin. Vasopressin also increased phosphorylation of NKCC2 at both Ser126 (more than fivefold) and Ser874 (more than threefold) in rats in vivo. Both sites were phosphorylated by purified protein kinase A during in vitro assays. These results support the view that, although protein kinase A plays a central role in mTAL signaling, additional kinases, including those that target proline-directed motifs, may be involved.
A family of diiron monooxygenases catalyzing amino acid beta-hydroxylation in antibiotic biosynthesis
Authors: Makris Thomas M. , Chakrabarti Mrinmoy , Münck Eckard , Lipscomb John D.
Published: August 2010

The biosynthesis of chloramphenicol requires a β-hydroxylation tailoring reaction of the precursor L-p-aminophenylalanine (L-PAPA). Here, it is shown that this reaction is catalyzed by the enzyme CmlA from an operon containing the genes for biosynthesis of L-PAPA and the nonribosomal peptide synthetase CmlP. EPR, Mössbauer, and optical spectroscopies reveal that CmlA contains an oxo-bridged dinuclear iron cluster, a metal center not previously associated with nonribosomal peptide synthetase chemistry. Single-turnover kinetic studies indicate that CmlA is functional in the diferrous state and that its substrate is L-PAPA covalently bound to CmlP. Analytical studies show that the product is hydroxylated L-PAPA and that O

2

is the oxygen source, demonstrating a monooxygenase reaction. The gene sequence of CmlA shows that it utilizes a lactamase fold, suggesting that the diiron cluster is in a protein environment not previously known to effect monooxygenase reactions. Notably, CmlA homologs are widely distributed in natural product biosynthetic pathways, including a variety of pharmaceutically important beta-hydroxylated antibiotics and cytostatics.
Proton and cation transport activity of the M2 proton channel from influenza A virus
Authors: Leiding Thom , Wang Jun , Martinsson Jonas , DeGrado William F. , Årsköld Sindra Peterson
Published: August 2010

The M2 protein is a small, single-span transmembrane (TM) protein from the influenza A virus. This virus enters cells via endosomes; as the endosomes mature and become more acidic M2 facilitates proton transport into the viral interior, thereby disrupting matrix protein/RNA interactions required for infectivity. A mystery has been how protons can accumulate in the viral interior without developing a large electrical potential that impedes further inward proton translocation. Progress in addressing this question has been limited by the availability of robust methods of unidirectional insertion of the protein into virus-like vesicles. Using an optimized procedure for reconstitution, we show that M2 has antiporter-like activity, facilitating K
+
or Na
+
efflux when protons flow down a concentration gradient into the vesicles. Cation efflux is very small except under conditions mimicking those encountered by the endosomally entrapped virus, in which protons are flowing through the channel. This proton/cation exchange function is consistent with the known high proton selectivity of the channel. Thus, M2 acts as a proton uniporter that occasionally allows K
+
to flow to maintain electrical neutrality. Remarkably, as the pH inside M2-containing vesicles (pH
in
) decreases, the proton channel activity of M2 is inhibited, but its cation transport activity is activated. This reciprocal inhibition of proton flux and activation of cation flux with decreasing pH
in
first allows accumulation of protons in the early stages of acidification, then trapping of protons within the virus when low pH
in
is achieved.
Heterodimeric integrin complexes containing β1-integrin promote internalization and lethality of anthrax toxin
Authors: Martchenko Mikhail , Jeong Sun-Young , Cohen Stanley N.
Published: August 2010

To kill macrophages, the lethal factor component of
Bacillus anthracis
toxin binds to a carrier protein (PA), which then interacts with the CMG2 receptor protein on the cell surface and is endocytosed into the cytoplasm. CMG2, as well as TEM8, a second PA receptor not present on macrophages, contain a von Willebrand A domain that is crucial for toxin binding. Here we report that integrin β1, another cell surface von Willebrand A domain protein, can mediate and potentiate anthrax toxin endocytosis. By using microarray-based analysis to globally correlate gene expression profiles with toxin sensitivity, we associated toxin effects with the integrin-activating proteins osteopontin and CD44. Further study showed that PA binds to α4β1– and α5β1–integrin complexes, leading to their conjoint endocytosis, and also interacts—weakly relative to CMG2 but comparably to TEM8—with purified α5β1 complex in vitro. Monoclonal antibody directed against β1-integrin or its α integrin partners reduced PA/integrin endocytosis and anthrax toxin lethality, and hyaluronic acid—which interferes with CD44-mediated integrin activation—had similar effects. Remarkably, whereas deficiency of CMG2 protected macrophages from rapid killing by large toxin doses (>50 ng/mL), by 24 h the toxin-treated cells were dead. Such late killing of CMG2-deficient cells by high dose toxin as well as the late death observed during exposure of CMG2-producing macrophages to low-dose toxin (<1 ng/mL), was dependent on integrin function. Effects of inactivating both CMG2 and integrin were synergistic. Collectively, our findings argue strongly that β1-integrin can both potentiate CMG2-mediated endocytosis and serve independently as a low-affinity PA receptor.
CpG island clusters and pro-epigenetic selection for CpGs in protein-coding exons of HOX and other transcription factors
Authors: Branciamore Sergio , Chen Zhao-Xia , Riggs Arthur D. , Rodin Sergei N.
Published: August 2010

CpG dinucleotides contribute to epigenetic mechanisms by being the only site for DNA methylation in mammalian somatic cells. They are also mutation hotspots and ∼5-fold depleted genome-wide. We report here a study focused on CpG sites in the coding regions of
Hox
and other transcription factor genes, comparing methylated genomes of
Homo sapiens
,
Mus musculus
, and
Danio rerio
with nonmethylated genomes of
Drosophila melanogaster
and
Caenorhabditis elegans.
We analyzed 4-fold degenerate, synonymous codons with the potential for CpG. That is, we studied “silent” changes that do not affect protein products but could damage epigenetic marking. We find that DNA-binding transcription factors and other developmentally relevant genes show, only in methylated genomes, a bimodal distribution of CpG usage. Several genetic code-based tests indicate, again for methylated genomes only, that the frequency of silent CpGs in
Hox
genes is much greater than expectation. Also informative are NCG-GNN and NCC-GNN codon doublets, for which an unusually high rate of G to C and C to G transversions was observed at the third (silent) position of the first codon. Together these results are interpreted as evidence for strong “pro-epigenetic” selection acting to preserve CpG sites in coding regions of many genes controlling development. We also report that DNA-binding transcription factors and developmentally important genes are dramatically overrepresented in or near clusters of three or more CpG islands, suggesting a possible relationship between evolutionary preservation of CpG dinucleotides in both coding regions and CpG islands.
Investment Readiness Programmes and Access to Finance: A Critical Review of Design Issues
Authors: Mason Colin , Kwok Jennifer
Published: August 2010

Access by SMEs to finance is constrained by demand-side weaknesses. Most businesses are not investment ready. Their owners are unwilling to seek external equity finance and those who are willing do not understand what equity investors are looking for or how to ‘sell’ themselves and their businesses to potential investors. These weaknesses, in turn, compromise the effectiveness of supply-side interventions, such as initiatives to stimulate business angels or which create public sector venture capital funds. This has highlighted the need for investment readiness programmes that seek to increase the pool of investable businesses. This paper reviews the design and delivery of investment readiness programmes in the UK and draws out lessons for best practice.
EPS Mid-Career Award 2009: From Observation to Action Simulation: The Role of Attention, Eye-Gaze, Emotion, and Body State
Authors: Tipper Steven P.
Published: August 2010

This paper reviews recent aspects of my research. It focuses, first, on the idea that during the perception of objects and people, action-based representations are automatically activated and, second, that such action representations can feed back and influence the perception of people and objects. For example, when one is merely viewing an object such as a coffee cup, the action it affords, such as a reach to grasp, is activated even though there is no intention to act on the object. Similarly, when one is observing a person's behaviour, their actions are automatically simulated, and such action simulation can influence our perception of the person and the object with which they interacted. The experiments to be described investigate the role of attention in such vision-to-action processes, the effects of such processes on emotion, and the role of a perceiver's body state in their interpretation of visual stimuli.
Modelling within Host Parasite Dynamics of Schistosomiasis
Authors: Chiyaka Edward T. , Magombedze Gesham , Mutimbu Lawrence
Published: August 2010

Schistosomiasis infection is characterized by the presence of adult worms in the portal and mesenteric veins of humans as part of a complex migratory cycle initiated by cutaneous penetration of the cercariae shed by infected freshwater snails. The drug praziquantel is not always effective in the treatment against schistosomiasis at larvae stage. However, our simulations show that it is effective against mature worms and eggs. As a result, the study and understanding of immunological responses is key in understanding parasite dynamics. We therefore introduce quantitative interpretations of human immunological responses of the disease to formulate mathematical models for the within‐host dynamics of schistosomiasis. We also use numerical simulations to demonstrate that it is the level of T cells that differentiates between either an effective immune response or some degree of infection. These cells are responsible for the differentiation and recruitment of eosinophils that are instrumental in clearing the parasite. From the model analysis, we conclude that control of infection is much attributed to the value of a function f, a measure of the average number of larvae penetrating a susceptible individual having hatched from an egg released by an infected individual. This agrees with evidence that there is a close association between the ecology, the distribution of infection and the disease.
Paradoxical buffering of calcium by calsequestrin demonstrated for the calcium store of skeletal muscle
Authors: Royer Leandro , Sztretye Monika , Manno Carlo , Pouvreau Sandrine , Zhou Jingsong , Knollmann Bjorn C. , Protasi Feliciano , Allen Paul D. , Ríos Eduardo
Published: August 2010

Contractile activation in striated muscles requires a Ca2+ reservoir of large capacity inside the sarcoplasmic reticulum (SR), presumably the protein calsequestrin. The buffering power of calsequestrin in vitro has a paradoxical dependence on [Ca2+] that should be valuable for function. Here, we demonstrate that this dependence is present in living cells. Ca2+ signals elicited by membrane depolarization under voltage clamp were compared in single skeletal fibers of wild-type (WT) and double (d) Casq-null mice, which lack both calsequestrin isoforms. In nulls, Ca2+ release started normally, but the store depleted much more rapidly than in the WT. This deficit was reflected in the evolution of SR evacuability, E, which is directly proportional to SR Ca2+ permeability and inversely to its Ca2+ buffering power, B. In WT mice E starts low and increases progressively as the SR is depleted. In dCasq-nulls, E started high and decreased upon Ca2+ depletion. An elevated E in nulls is consistent with the decrease in B expected upon deletion of calsequestrin. The different value and time course of E in cells without calsequestrin indicate that the normal evolution of E reflects loss of B upon SR Ca2+ depletion. Decrement of B upon SR depletion was supported further. When SR calcium was reduced by exposure to low extracellular [Ca2+], release kinetics in the WT became similar to that in the dCasq-null. E became much higher, similar to that of null cells. These results indicate that calsequestrin not only stores Ca2+, but also varies its affinity in ways that progressively increase the ability of the store to deliver Ca2+ as it becomes depleted, a novel feedback mechanism of potentially valuable functional implications. The study revealed a surprisingly modest loss of Ca2+ storage capacity in null cells, which may reflect concurrent changes, rather than detract from the physiological importance of calsequestrin.
Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node
Authors: Liao Zhandi , Lockhead Dean , Larson Eric D. , Proenza Catherine
Published: August 2010

The sympathetic nervous system increases heart rate by activating β adrenergic receptors and increasing cAMP levels in myocytes in the sinoatrial node. The molecular basis for this response is not well understood; however, the cardiac funny current (If) is thought to be among the end effectors for cAMP signaling in sinoatrial myocytes. If is produced by hyperpolarization-activated cyclic nucleotide–sensitive (HCN4) channels, which can be potentiated by direct binding of cAMP to a conserved cyclic nucleotide binding domain in the C terminus of the channels. β adrenergic regulation of If in the sinoatrial node is thought to occur via this direct binding mechanism, independent of phosphorylation. Here, we have investigated whether the cAMP-activated protein kinase (PKA) can also regulate sinoatrial HCN4 channels. We found that inhibition of PKA significantly reduced the ability of β adrenergic agonists to shift the voltage dependence of If in isolated sinoatrial myocytes from mice. PKA also shifted the voltage dependence of activation to more positive potentials for heterologously expressed HCN4 channels. In vitro phosphorylation assays and mass spectrometry revealed that PKA can directly phosphorylate at least 13 sites on HCN4, including at least three residues in the N terminus and at least 10 in the C terminus. Functional analysis of truncated and alanine-substituted HCN4 channels identified a PKA regulatory site in the distal C terminus of HCN4, which is required for PKA modulation of If. Collectively, these data show that native and expressed HCN4 channels can be regulated by PKA, and raise the possibility that this mechanism could contribute to sympathetic regulation of heart rate.
Airway surface liquid depth imaged by surface laser reflectance microscopy
Authors: Thiagarajah Jay R. , Song Yuanlin , Derichs Nico , Verkman A.S.
Published: August 2010

The thin layer of liquid at the surface of airway epithelium, the airway surface liquid (ASL), is important in normal airway physiology and in the pathophysiology of cystic fibrosis. At present, the best method to measure ASL depth involves scanning confocal microscopy after staining with an aqueous-phase fluorescent dye. We describe here a simple, noninvasive imaging method to measure ASL depth by reflectance imaging of an epithelial mucosa in which the surface is illuminated at a 45-degree angle by an elongated 13-µm wide rectangular beam produced by a 670-nm micro-focus laser. The principle of the method is that air–liquid, liquid–liquid, and liquid–cell interfaces produce distinct specular or diffuse reflections that can be imaged to give a micron-resolution replica of the mucosal surface. The method was validated using fluid layers of specified thicknesses and applied to measure ASL depth in cell cultures and ex vivo fragments of pig trachea. In addition, the method was adapted to measure transepithelial fluid transport from the dynamics of fluid layer depth. Compared with confocal imaging, ASL depth measurement by surface laser reflectance microscopy does not require dye staining or costly instrumentation, and can potentially be adapted for in vivo measurements using fiberoptics.
Estimation of upper bounds for the applicability of non-linear similarity functions for non-dimensional wind and temperature profiles in the surface layer in very stable conditions
Authors: Sharan Maithili , Kumar Pramod
Published: August 2010

The computation of surface fluxes by Monin–Obukhov similarity theory with different linear/non-linear similarity functions for non-dimensional wind and temperature profiles becomes limited to specific ranges of
ζ
=
z
/
L
(where
z
is the height above ground and
L
is the Obukhov length) and bulk Richardson number (
Ri
B
) under very stable conditions. A systematic mathematical analysis is carried out to estimate the upper bounds of
ζ
and
Ri
B
for the extent of applicability of different non-linear similarity functions in the surface layer under these conditions. A generalized methodology is proposed on the basis of momentum drag coefficient (
C
D
) and heat exchange coefficient (
C
H
) and applied to various non-linear similarity functions available in the literature. A theoretically derived criterion for the applicability of each of the non-linear similarity function is evaluated with observations from Cooperative Atmosphere-Surface Exchange Study-99 and UK Meteorological Office’s Cardington datasets. The evaluation with both datasets for each non-linear similarity function confirms the validity of proposed theoretical results under very stable conditions.
Delayed Parenthood and the Risk of Cesarean Delivery—Is Paternal Age an Independent Risk Factor?
Authors: Tang Chao‐Hsiun , Wu Ming‐Ping , Liu Jin‐Tan , Lin Herng‐Ching , Hsu Chun‐Chyang
Published: August 2010

Abstract:  Background:
Between 1995 and 2001, the average cesarean section rates in Taiwan were as high as 33.34 percent. This study set out to determine the independent effects of paternal age on the likelihood of cesarean delivery among a sample of Taiwanese women. Methods:Logistic regressions were used to analyze 310,574 singleton deliveries by nulliparous women in Taiwan between 1999 and 2001, linking data abstracted from birth certificates and from the National Health Insurance claims database. After controlling for socioeconomic, pregnancy, and obstetric complications, as well as institutional factors, we investigated both maternal and paternal ages simultaneously, using the single category variable “parental age” to determine the differential age effects on the risk of cesarean delivery. Results:Taking 20‐ to 29‐year‐old couples as the reference group, we observed that the relative risks of cesarean delivery become progressively higher with advancing age of the mother. At the same time, within each maternal group, positive and significant variations in cesarean rates occurred for different paternal age groups. The respective increases in the relative risks of cesarean delivery for men aged 20–29, 30–34, 35–39, and 40 years or more, in conjunction with women aged 20–29, 30–34 and 35 or over, are 34 percent from 1.00 to 1.34, 18 percent from 1.51 to 1.69, and 16 percent from 2.03 to 2.19. Other confounding variables are also taken into account. Conclusions:Irrespective of maternal age, advancing paternal age also appears to be an additional independent factor that has a strong association with the increase in cesarean section rates. (BIRTH 33:1 March 2006)
Prospective Testing of the Brisbane Postnatal Depression Index
Authors: Webster Joan , Hall Laurie , Somville Thierry , Schneider Patricia , Turnbull Robin , Smith Patricia
Published: August 2010

Abstract:  Background:
Over 50 percent of women have one or more risk factors for postnatal depression during pregnancy or in the perinatal period, but only 10 to 15 percent become clinically depressed. The objective of this study was to prospectively test the Brisbane Postnatal Depression Index (referred to here as Index), to validate a theoretical index that was developed earlier, and to establish whether the index could be introduced as a clinically useful method to detect women who may be at risk for developing postnatal depression.
Methods:
Antenatally, women were asked about social support and about personal and family history of mental illness, including postnatal depression. Responses were scored according to predefined ratings on the Index. In the postnatal wards, 353 women were recruited and their scores for “blues,” social support, feelings about the baby, and satisfaction with the birth process were added. Sixteen weeks after hospital discharge, women were asked to complete the Edinburgh Postnatal Depression Scale. The Brisbane Index was validated by the number of women scoring more than 12 on the Edinburgh Postnatal Depression Scale at 16 weeks postpartum who were correctly predicted by a score of more than 6 on the Index. Sensitivity, specificity, positive predictive value, and negative predictive value for the Index, using >6 as a cutoff point, were calculated. “Ease of use” was assessed informally with participants and staff responsible for administration and scoring the instrument.
Results:
Compared with results from the derivation study, prospective testing of the index showed an improvement in sensitivity from 36.3 to 47.5 percent and a small decrease in specificity, but no improvement on the positive predictive value from 39.8 to 39.6 percent.
Conclusion:
The Brisbane Postnatal Depression Index was validated in a prospective sample, but its sensitivity and specificity require improvement before introduction as a measure of prediction. (BIRTH 33:1 March 2006)