bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling payback from research into the efficacy of left-ventricular assist devices as destination therapy
Authors: Girling Alan J. , Freeman Guy , Gordon Jason P. , Poole-Wilson Philip , Scott David A. , Lilford Richard J.
Published: April 2007

Objectives:Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis.

Methods:Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field.

Results:Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (∼.2 percent) for devices costing as much as £60,000. Sensitivity of the conclusions to both device cost and QALY valuation is examined.

Conclusions:In the event that the price of the device in use would reduce to £40,000, the value of the survival information can readily justify investment in further trials.
Diffusion of magnetic resonance imaging in Iran
Authors: Palesh Mohammad , Fredrikson Sten , Jamshidi Hamidreza , Jonsson Pia Maria , Tomson Goran
Published: April 2007

Objectives:The aim of this article is to describe the diffusion of magnetic resonance imaging (MRI) in Iran, including regional variations during the period of 1990 to 2005 and international comparisons.

Methods:Data on the diffusion of MRI were obtained from the Medical Equipment Office of the Ministry of Health (MOH) and, using self-administered questionnaires, from forty-one universities specializing in medical sciences. Data were gathered from the year of first purchase up to mid-2005. Information for international comparisons was obtained from the Organization for Economic Cooperation and Development health data of 2006.

Results:Iran purchased its first MRI unit in 1990. Since then, the number of MRI units has increased remarkably. The diffusion curve of MRI in Iran follows an S-shaped curve with a very slow speed in the period of 1991–95. Accelerated adoption occurred later coinciding with a significant influence from the private sector, especially from 1999. Iran had ninety-three MRI units in 2005, and the number of MRI units per million in the population was 1.36.

Conclusions:The number of MRI units in provinces is not in direct proportion to the number of their inhabitants. Rational adoption and equitable diffusion of MRI may require the MOH and regulatory bodies to improve their ability in health technology assessment and integrate it into the policy making regarding adoption, diffusion, and utilization of health technologies.
Pattern and factors leading to the diffusion of magnetic resonance imaging in Korean hospitals
Authors: Hahm Myung-Il , Park Eun-Cheol , Lee Sun-Hee , Nam Chung Mo , Kang Hye-Young , Lee Hoo-Yeon , Cho Woo-Hyun
Published: April 2007

Objectives: The purpose of this study was to examine the diffusion patterns of new medical technologies in Korean hospitals. We also sought to identify critical factors leading to the decision to acquire capital-intensive medical technology. The rationale and timing of magnetic resonance imaging (MRI) acquisitions were retrospectively evaluated according to a “whether, when, and why” paradigm.

Methods: We analyzed data pertaining to 232 hospitals with active medical residency programs. Of these, 185 hospitals owned or leased an MRI unit, and 47 had not acquired units as of June 2004. Data were collected from the Ministry of Health and Welfare, Korean National Statistical Office, and Korean Hospital Association databases, and variables were identified and classified as predisposing, enabling, or reinforcing factors.

Results: The MRI diffusion rate curve was linear for two types of hospital but was S-shaped for tertiary hospitals, which were early adopters of MRI. Significant predictors for MRI adoption included the per capita number of regional physicians (+), total number of existing regional MRI units (−), percentage of the regional population over 65 years of age (+), private ownership of the hospital, presence of a radiology residency program, number of beds (+), and regional per capita taxable income (+).

Conclusions: Diffusion of MRI technology is occurring rapidly across Korean hospitals. The factors affecting MRI adoption in Korea are similar to the factors documented in other countries, namely regional population over age 65, regional income per capita, large hospitals, and teaching hospitals. This study provides baseline information for predicting diffusion patterns of other new and/or expensive medical technologies.
Vladko Maček and the Croat Political Right, 1928–1941
Authors: BIONDICH MARK
Published: April 2007

The Croat Peasant Party was arguably the most important Croatian political party during the existence of the first Yugoslavia (1918–41). Under the leadership of Vladko Maček (1879–1964), it entered the most difficult period of its history: it was forced to contend with the royal dictatorship (1929–34) of King Aleksandar Karadjordjević, the Great Depression, growing nationality tensions and an increasingly volatile political climate in which the extremes of the right and left, represented in Croatia by the Ustaša and Communist parties respectively, contended for power. This article examines the contentious relationship between Maček's Croat Peasant Party and the fascist Ustaša movement between 1929 and 1941, and assesses Maček's legacy and his place in Croatia's 20th-century political history.
War and Genocide on the Eastern Front, 1941–1945
Authors: NAIMARK NORMAN M.
Published: April 2007

The historical connection between war and genocide is clear and apparent. Scholars of mass killing have repeatedly pointed out the linkages between the First World War and the Armenian genocide of 1915, between the Second World War and the Holocaust, between the 1993–4 war and the genocide in Rwanda, and between the war in Bosnia and the genocide in Srebrenica. Scholars of war, most often military historians, have been less ready to tie what they see as two distinct social phenomena – war and genocide – into the same bundle. This was especially the case, until recently, for the Nazi attack on the Soviet Union on 22 June 1941, and the subsequent mass murder of the Jews. The Wehrmacht, the German fighting forces, were seen to be implementing an enormously ambitious military campaign against the Soviet Union, which, in the end, they lost. Meanwhile, the Nazi security organs – the SS, the SD, and the Einsatzgruppen – carried out the ‘Final Solution’, inspired primarily by Hitler and the Nazi hierarchs.
Pollination of exoplanets by nebulae
Authors: Napier W.M.
Published: April 2007

The Solar System passes within 5 pc of star-forming nebulae every ∼50–100 million years, a distance which can be bridged by protected micro-organisms ejected from the Earth by impacts. Such encounters disturb the Oort cloud, and induce episodes of bombardment of the Earth and the ejection of microbiota from its surface. Star-forming regions within the nebulae encountered may thus be seeded by significant numbers of microorganisms. Propagation of life throughout the Galactic habitable zone ‘goes critical’ provided that, in a typical molecular cloud, there are at least 1.1 habitable planets with impact environments similar to that of the Earth. Dissemination of microbiota proceeds most rapidly through the molecular ring of the Galaxy.
Geodetic and geophysical results from a Taiwan airborne gravity survey: Data reduction and accuracy assessment
Authors: Hwang Cheinway , Hsiao Yu‐Shen , Shih Hsuan‐Chang , Yang Ming , Chen Kwo‐Hwa , Forsberg Rene , Olesen Arne V.
Published: April 2007

An airborne gravity survey was conducted over Taiwan using a LaCoste and Romberg (LCR) System II air‐sea gravimeter with gravity and global positioning system (GPS) data sampled at 1 Hz. The aircraft trajectories were determined using a GPS network kinematic adjustment relative to eight GPS tracking stations. Long‐wavelength errors in position are reduced when doing numerical differentiations for velocity and acceleration. A procedure for computing resolvable wavelength of error‐free airborne gravimetry is derived. The accuracy requirements of position, velocity, and accelerations for a 1‐mgal accuracy in gravity anomaly are derived. GPS will fulfill these requirements except for vertical acceleration. An iterative Gaussian filter is used to reduce errors in vertical acceleration. A compromising filter width for noise reduction and gravity detail is 150 s. The airborne gravity anomalies are compared with surface values, and large differences are found over high mountains where the gravity field is rough and surface data density is low. The root mean square (RMS) crossover differences before and after a bias‐only adjustment are 4.92 and 2.88 mgal, the latter corresponding to a 2‐mgal standard error in gravity anomaly. Repeatability analyses at two survey lines suggest that GPS is the dominating factor affecting the repeatability. Fourier transform and least‐squares collocation are used for downward continuation, and the latter produces a better result. Two geoid models are computed, one using airborne and surface gravity data and the other using surface data only, and the former yields a better agreement with the GPS‐derived geoidal heights. Bouguer anomalies derived from airborne gravity by a rigorous numerical integration reveal important tectonic features.
Observations of upper ocean boundary layer dynamics in the marginal ice zone
Authors: Fer Ilker , Sundfjord Arild
Published: April 2007

Vertical profiles of turbulent kinetic energy dissipation and small‐scale hydrography were collected in the upper ocean boundary of both ice‐covered and ice‐free stations in the marginal ice zone of the Barents Sea in spring 2005. Together with shipboard wind measurements and current profiles, the mixed and mixing layer dynamics are studied. During the survey, shear production by the stress at the surface or under the ice dominated. Large upward turbulent heat fluxes ∼300–500 W m−2 were calculated for the mixing layers overlying the warm Atlantic Water which compared well with those obtained from an independent parameterization. At the top of the pycnocline, corresponding heat fluxes were 10–20 W m−2. Significant stabilizing buoyancy fluxes were estimated for ice‐drift stations owing to the melting of ice in response to the large heat fluxes. The mean dissipation profile in the ice‐free reference station agreed with the constant‐stress wall layer scaling within 30%. On the contrary, the observed dissipation profiles were enhanced in the upper half of under‐ice mixing layer or within 2.5 times the assessed pressure‐ridge keel depth. Deeper in the mixing layer the profiles relaxed toward the wall scaling. The variability of dissipation in the mixed layer was better captured by the shear production profile when local friction speed was used together with a mixing length profile modified by buoyancy fluxes. Significant correlations were found between dissipation integrated over the mixing layer and work done by stress under the ice and the wind work at 10 m height. The low correlation between the mixed layer depth and length scale for neutral conditions significantly increased when the reduction in the mixing length due to buoyancy fluxes was accounted for. The mixing depth is observed to be strongly correlated with the outer neutral planetary length scale.
Indications of a link between seismotectonics and CH4 release from seeps off Costa Rica
Authors: Mau Susan , Rehder Gregor , Arroyo Ivonne G. , Gossler Jürgen , Suess Erwin
Published: April 2007

Measurements of CH4 concentrations in the bottom water during two discrete sampling periods in subsequent years above different cold seeps at the Pacific margin off Costa Rica indicate large‐scale variations of CH4 release. CH4 is emitted from mud extrusions and a slide scar at 1000–2300 m water depth. Maximum CH4 concentrations were found to be lower above all investigated sites in autumn 2003 than in autumn 2002 although seep sites are up to 300 km apart. Tidal and current changes were observed but found to apply only to individual seep sites. Increased seismic activity connected to the moment magnitude (MW) 6.4 earthquake offshore Costa Rica in June 2002 could have had an impact on all seep sites and thereby caused an increase in CH4 emission. This is supported by the largest variations of CH4 concentration found above mud extrusions located above faults likely more strongly affected by tectonic movements. Even though our data indicate a relation between seismicity and CH4 seepage, the relation is not proven, and future work is needed to comprehensively test this hypothesis.
Assessing consistency between EOS MLS and ECMWF analyzed and forecast estimates of cloud ice
Authors: Li J.‐L. , Jiang J. H. , Waliser D. E. , Tompkins A. M.
Published: April 2007

Cloud ice water content (IWC) from MLS retrievals and ECMWF analyses and forecasts are compared for August 2004 to July 2005. ECMWF data are sampled along MLS tracks and filtered according to MLS sensitivity. At 147 hPa, there is good spatial agreement with the analyses biased high by 10%. Over landmasses, the analyses are biased low up to 50%. This underestimation grows in the forecasts, with a 40% reduction by day 10. At 215 hPa, the analyses are biased low by 10–60%. However, at this level the forecast IWC undergoes little change. These biases, in conjunction with those in precipitation and top of the atmosphere radiative fluxes, along with consideration of the changes in vertical velocity, cumulus cloud mass flux and cloud top detrainment, indicates a systematic reduction of the modeled deep convection over the warm pool in conjunction with a weakened large‐scale circulation and enhanced upper‐level vertical stratification.
Stress, strain, and B‐type olivine fabric in the fore‐arc mantle: Sensitivity tests using high‐resolution steady‐state subduction zone models
Authors: Kneller E. A. , van Keken P. E. , Katayama I. , Karato S.
Published: April 2007

Shear‐wave splitting observations at several subduction systems show trench‐parallel fast directions in the fore‐arc mantle. The presence of B‐type olivine fabric in the mantle wedge may provide an explanation for this pattern of anisotropy under low‐temperature and hydrated conditions. Sensitivity tests are shown that provide insights into the distribution and magnitude of B‐type fabric using two‐dimensional, high‐resolution, kinematic‐dynamic subduction zone models. These models include a wet olivine rheology and a simulated aseismic creep zone in the fore‐arc mantle with parameterized viscous coupling between the slab and mantle wedge. The calculated thermal structure is in reasonable agreement with heat flow observations and Q tomography for small amounts of coupling and moderate amounts of shear heating in the seismogenic and aseismic creep zones. These small amounts of viscous coupling give rise to a slowly flowing fore‐arc mantle with thermal, stress, and strain conditions suitable for significant B‐type fabric development. The minimum shear stress necessary to drive geologically significant flow in the predicted B‐type region is sensitive to the magnitude of shear heating along the aseismic creep zone and ranges from less than 100 to 300 MPa. The minimum time required to generate sufficient finite strain for fabric development in the B‐type region is around 10 Myr depending on the amount of coupling and shear heating. The predicted distribution of olivine fabric is consistent with a pattern of shear wave anisotropy with trench‐parallel fast polarization directions above the fore arc and a rapid rotation to trench‐perpendicular in the arc and back arc.
Soil uptake of carbonyl sulfide in subtropical forests with different successional stages in south China
Authors: Yi Zhigang , Wang Xinming , Sheng Guoying , Zhang Deqiang , Zhou Guoyi , Fu Jiamo
Published: April 2007

The uptake rates of carbonyl sulfide (COS) by soils in subtropical forests with different successional stages were measured using static chambers in Dinghushan Biosphere Reserve (DBR) in south China from July 2004 to March 2005. The three typical tropical forests studied included monsoon evergreen broad‐leaf forest (BF), pine and broad‐leaf mixed forest (MF) and pine forest (PF), representing forests with different succession stages in the region. COS exchange rates were also compared between the plots with litter‐fall remaining (plots L) and those with litter‐fall removed (plots S) in each forest. Results showed that these forest soils all acted as sinks for COS with exchange rates of −1.22 to −11.82 pmol m−2 s−1. The MF in the midsuccessional stage had significantly higher uptake rates, and the mean exchange rates in the BF, MF, and PF were −3.90, −4.77, and −3.65 pmol m−2 s−1, respectively. COS uptake rates at plots L were higher than those at plots S. Mean COS fluxes were significantly higher in March (−6.06 pmol m−2 s−1) than those in July (−3.60 pmol m−2 s−1), August (−3.82 pmol m−2 s−1), September (−3.45 pmol m−2 s−1), and October (−3.54 pmol m−2 s−1). Significant correlation was observed between the COS uptake rates and soil respiration rates or microbial biomass, indicating that microbial activity was an important factor controlling the soil uptake of COS. Significant correlations between COS fluxes and initial COS mixing ratios were only observed in the BF and MF. COS fluxes showed no correlation with soil temperature or water content alone in any of the three forests, but do correlate well with soil temperature and water content together in polynomial forms with an order of 2.
Martian Dunite NWA 2737: Petrographic constraints on geological history, shock events, and olivine color
Authors: Treiman Allan H. , Dyar M. Darby , McCanta Molly , Noble Sarah K. , Pieters Carle M.
Published: April 2007

Meteorite Northwest Africa (NWA) 2737 is the second known chassignite, an olivine‐rich igneous rock with mineral compositions and isotopic ratios that suggest it formed on Mars. NWA 2737 consists of ∼85% vol. olivine (Mg#, molar Mg/(Mg + Fe), of 78.3 ± 0.4%), which is notable because it is black in hand sample and brown in thin section. Other minerals include chromite, pyroxenes (augite, pigeonite, orthopyroxene), and diaplectic glass of alkali‐feldspar composition. Aqueous alteration is minimal and appears only as slight dissolution of glass. NWA 2737 formed by accumulation of olivine and chromite from a basaltic magma; the other minerals represent magma trapped among the cumulus grains. Minerals are compositionally homogeneous, consistent with chemical equilibration in late and postigneous cooling. Two‐pyroxene thermometry gives equilibration temperatures ∼1150°C, implying a significant time spent at the basalt solidus. Olivine‐spinel‐pyroxene equilibria give ∼825°C (possibly the T of mesostasis crystallization) at an oxidation state of ∼QMF‐1. This oxidation state is consistent with low Fe3+ in olivine (determined by EMP, Mössbauer spectra, and synchrotron micro‐XANES spectroscopy) and with ∼10% of the iron in pyroxene being Fe3+. NWA 2737 experienced two shock events. The first shock, to stage S5–S6, affected the olivine by producing in it planar deformation features, intense mosaicism and lattice strain, and abundant droplets of iron‐nickel metal, 5–15 nm in diameter. At this stage the olivine became deeply colored, i.e., strongly absorbing at visible and near‐infrared (NIR) wavelengths. This shock event and its thermal pulse probably occurred at ∼170 Ma, the Ar‐Ar age of NWA 2737. The colored olivine is cut by ribbons of coarser, uncolored olivine with long axes along [100] and shorter axes on {021} planes: These are consistent with the easy slip law for olivine [100]{021}, which is activated at moderate strain rate at high temperature. Within these ribbons the olivine was coarsened and the iron metal globules coalesced to micron‐sized grains. The ribbons also are mosaicized and cut by planar fractures, which bespeak a second shock event, possibly that of ejection from Mars. The deeply colored olivine in NWA 2737 is unusual and represents a new “ground truth” type for remote sensing of Mars. Understanding the occurrence of the brown color in olivine in NWA 2737 places important constraints on interpretation of optical measurements.
Electron precipitation from the inner radiation belt above Arecibo
Authors: Pradipta R. , Labno A. , Lee M. C. , Burke W. J. , Sulzer M. P. , Cohen J. A. , Burton L. M. , Kuo S. P. , Rokusek D. L.
Published: April 2007

We examine possible correlations between occurrences of nighttime E‐region plasma line (PL) enhancements over Arecibo and 40.75 kHz NAU emissions. On the night of January 1–2, 2006, the experiments were conducted from 22:00 to 6:00 local time (LT). NAU transmitter was initially turned off until 01:45 LT, when continuous operations resumed for the remainder of the experiments. Enhanced PL events lasting <10 s had central frequencies and bandwidths of about 2.5 and 1.5 MHz, respectively, indicating that Arecibo radar detected 2.3 to 8.5 eV suprathermal electrons streaming along geomagnetic fields. The rate of PL event detections increased by a factor of 2.8 after NAU turn‐on. We suggest that 40.75 kHz radiation sporadically leaked though local ionosphere, probably abetted by field‐aligned irregularities. The radiation propagated in whistler mode into the L = 1.35 inner radiation belt where gyroresonant interactions with trapped 390 keV electrons increased the precipitation rate.
Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell mitogenesis
Authors: Yao J , Zhu Y , Sun W , Sawada N , Hiramatsu N , Takeda M , Kitamura M
Published: April 2007

Background and purpose:

Deficiency in nitric oxide (NO) is a major factor leading to deterioration and progression of certain glomerular diseases. Agents enhancing NO availability and potentiality are renoprotective. Irsogladine maleate (IM), an anti‐ulcer drug, is reported to improve gastric blood flow via NO‐dependent mechanisms. We, therefore, asked whether and how IM interacted with NO on glomerular mesangial cells.

Experimental approach:

Mesangial cells were exposed to IM and NO donors. Activation of cAMP signalling pathways was assessed by intracellular cAMP, phosphorylation of VASP, activation of the cAMP response element (CRE) and expression of CRE‐regulated proteins.

Key results:

IM alone did not affect cell proliferation. However, it greatly enhanced the growth‐inhibitory effect of NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP). IM acted synergistically with NO on suppression of mitogen‐activated protein kinase activation, induction of gap junction protein connexin43, increase of intracellular cAMP, and phosphorylation of VASP. With the use of the CRE‐SEAP‐based reporting system, IM and SNAP cooperatively activated cAMP response elements (CRE). A similar activation of cAMP was induced by IM with two different NO donors, the sGC activator Bay 41‐2272 and the cGMP analogue 8‐bromo‐cGMP. The effects of SNAP and IM on cAMP activation were mimicked by phosphodiesterase 3 (PDE3) and PDE4 inhibitors. In addition, IM markedly augmented cytokine‐induced expression of iNOS, production of NO and activation of CRE.

Conclusion and implications:

The effects of NO were greatly potentiated by IM through synergistic activation of cAMP pathway. Combined therapy with IM and NO may be developed for certain renal diseases.

British Journal of Pharmacology (2007) 151, 457–466; doi:10.1038/sj.bjp.0707255
Non‐steroidal anti‐inflammatory drugs increase insulin release from beta cells by inhibiting ATP‐sensitive potassium channels
Authors: Li J , Zhang N , Ye B , Ju W , Orser B , Fox J E M , Wheeler M B , Wang Q , Lu W‐Y
Published: April 2007

Background and purpose:

Some non‐steroidal anti‐inflammatory drugs (NSAIDs) incidentally induce hypoglycemia, which is often seen in diabetic patients receiving sulphonylureas. NSAIDs influence various ion channel activities, thus they may cause hypoglycemia by affecting ion channel functions in insulin secreting beta cells. This study investigated the effects of the NSAID meclofenamic acid (MFA) on the electrical excitability and the secretion of insulin from pancreatic beta cells.

Experimental approach:

Using patch clamp techniques and insulin secretion assays, the effects of MFA on the membrane potential and transmembrane current of INS‐1 cells, and insulin secretion were studied.

Key results:

Under perforated patch recordings, MFA induced a rapid depolarization in INS‐1 cells bathed in low (2.8mM), but not high (28mM) glucose solutions. MFA, as well as acetylsalicylic acid (ASA) and flufenamic acid (FFA), excited the cells by inhibiting ATP‐sensitive potassium channels (KATP). In whole cell recordings, KATPconductance consistently appeared when intracellular ATP was diluted. Intracellular glibenclamide prevented the development of KATPactivity, whereas intracellular MFA had no effect. At low glibenclamide concentrations, MFA induced additional inhibition of the KATPcurrent. Live cell Ca2+imaging displayed that MFA elevated intracellular Ca2+at low glucose concentrations. Furthermore, MFA dose‐dependently increased insulin release under low, but not high, glucose conditions.

Conclusions and Implications:

MFA blocked KATPthrough an extracellular mechanism and thus increased insulin secretion. As some NSAIDs synergistically inhibit KATPactivity together with sulphonylureas, the risk of NSAID‐induced hypoglycemia should be considered when glucose‐lowering compounds are administered.

British Journal of Pharmacology(2007)151, 483–493; doi:10.1038/sj.bjp.0707259
Visual Analytics: Why Now?
Authors: Thomas James (Jim) J.
Published: April 2007

An emerging field of study, visual analytics, is briefly described, including its motivations and the emerging partnerships that are bringing the best talents and technologies to missions such as homeland security and human health.
Synthesis, Relaxivity, and T1 Relaxation Enhancement of Binuclear Gadolinium(III) Complexes Based on DTPA or EDTA and Long-Chain Alkyl Esters of L-Lysine
Authors: Yu Kaichao , Hamdan Yousef , Wan Fuxian , Li Yinxia , Huang Kaixun , Zhou Jinlan
Published: April 2007

Eight novel diamino-ester ligands were synthesized by amidation reaction of long-chain alkyl esters of l-lysine with diethylenetriamine pentaacetic acid monoanhydride or ethylenediamine tetraacetic acid monoanhydride. The corresponding dimeric Gd(iii) complexes were obtained by treating these ligands with GdCl3·6H2O. All ligands and complexes were characterized by 1H NMR, FT-IR, and elemental analysis. The longitudinal relaxation time (T1) was measured, and all relaxivity values (R1) of these dimeric Gd(iii) complexes are higher than that of Magnivest (Gd-DTPA). One of these complexes, possessing the highest relaxivity in the DTPA series, was chosen to test the acute toxicity and T1-weighted imaging. It was found that this dimeric Gd(iii) complex exhibits no acute toxicity, and offers highly enhanced MRI signal and increases intention time in the rat liver tissue compared to Magnivest.
Room-Temperature Structure of Ammonia Borane
Authors: Bowden Mark E. , Gainsford Graeme J. , Robinson Ward T.
Published: April 2007

Structural determinations of ammonia borane (BH3NH3) have been carried out for the orthorhombic (at 90 K) and tetragonal (at 298 K) modifications using single-crystal X-ray data. The orthorhombic structure (space group Pmn21) agreed with a previously published neutron determination, while the tetragonal structure (I4mm) exhibited halos of hydrogen atom occupancy around both the nitrogen and boron atoms. The bond angles to the regions of hydrogen occupancy are consistent with the expected tetrahedral geometry for –BH3 and –NH3 groups. A new model for tetragonal BH3NH3 was constructed which accounts for the hydrogen disorder in the I4mm structure while introducing only weak new diffraction peaks. These peaks could not be found, however, and it is likely that the hydrogen disorder in tetragonal BH3NH3 arises from either rotations of higher than 3-fold order, or from random orientations of hydrogen-containing groups.
Synthesis and Characterization of Some Novel Homo- and Hetero-Diradicals of Hydrazyl and Nitroxide Type
Authors: Ionita Petre , Tuna Floriana , Andruh Marius , Constantinescu Titus , Balaban Alexandru T.
Published: April 2007

Starting from the well known stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH; 2a) and its congener 2,2-diphenyl-1-(4-cyano-2,6-dinitrophenyl)hydrazyl 2b, or from their reduced hydrazine counterparts 1a,b, it was possible to obtain the p-quinonoid compounds 4a,b by oxidation with ceric (Ce4+) sulfate, which by reduction gave the corresponding hydroxyl derivatives 2-phenyl-2-(4-hydroxyphenyl)-1-picrylhydrazine 5a or 2-phenyl-2-(4-hydroxyphenyl)-1-(4-cyano-2,6-dinitrophenyl)hydrazine 5b. These hydroxyl derivatives (5a,b) react with 4-carboxy-TEMPO or 2,2-diphenyl-1-(4-carboxy-2,6-dinitrophenyl)hydrazine to form the corresponding esters 6a,b or 8a,b. These esters (6a,b and 8a,b) lead to the hybrid hetero diradicals (nitroxide–hydrazyl type) 7a,b or homo biradicals (hydrazyl–hydrazyl type) 9a,b by oxidation with lead dioxide or potassium permanganate. The new compounds were characterized by UV-vis, NMR, EPR, and MS analysis, and their magnetic behaviour was investigated.
Synthesis, Characterization, and Crystal Structures of Three cis/trans Pyridine - Cyclopalladated Ferrocenylimine Complexes, and Their Catalysis in Suzuki Reactions
Authors: Xu Chen , Gong Jun-Fang , Zhang Yan-Hui , Zhu Yu , Wu Yang-Jie
Published: April 2007

Three new pyridine–cyclopalladated ferrocenylimine complexes 2a–c have been easily prepared and characterized by elemental analysis, ESI-MS, 1H NMR, and IR spectra. Their detailed structures are determined by single-crystal X-ray analysis. Palladacycle 2a is found to be a cis complex in the solid state, while 2b and 2c are trans complexes. These complexes were found to be efficient for the Suzuki reaction of aryl bromides with phenylboronic acid. Typically, using 0.2 mol% of 2c in the presence of 1.5 equivalents of K2CO3 as base in toluene at 100°C provided the coupled products in good to excellent yields.
An Expeditious Synthesis of Isofagomine
Authors: Goddard-Borger Ethan D. , Stick Robert V.
Published: April 2007

An expeditious synthesis of isofagomine, from d-arabinose, is reported.
α-Phenylethyl Substituted Bis(pivaloyloxymethyl) Ester Analogues of Fosmidomycin and FR900098
Authors: Kurz Thomas , Behrendt Christoph , Kaula Uwe , Bergmann Bärbel , Walter Rolf D.
Published: April 2007

α-Phenylethyl substituted bis(pivaloyloxymethyl) ester analogues of the natural products Fosmidomycin and FR900098 have been synthesized, and their in vitro antimalarial activity determined. The α-phenylethyl substituted Fosmidomycin analogue displays moderate in vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum.
CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-κB activation
Authors: Grabiner Brian C. , Blonska Marzenna , Lin Pei-Chun , You Yun , Wang Donghai , Sun Jiyuan , Darnay Bryant G. , Dong Chen , Lin Xin
Published: April 2007

G protein-coupled receptors (GPCRs) play pivotal roles in regulating various cellular functions. Although many GPCRs induce NF-κB activation, the molecular mechanism of GPCR-induced NF-κB activation remains largely unknown. CARMA3 (CARD and MAGUK domain-containing protein 3) is a scaffold molecule with unknown biological functions. By generating CARMA3 knockout mice using the gene targeting approach, here we show CARMA3 is required for GPCR-induced NF-κB activation. Mechanistically, we found that CARMA3 deficiency impairs GPCR-induced IκB kinase (IKK) activation, although it does not affect GPCR-induced IKKα/β phosphorylation, indicating that inducible phosphorylation of IKKα/β alone is not sufficient to induce its kinase activity. We also found that CARMA3 is physically associated with NEMO/IKKγ, and induces polyubiquitination of an unknown protein(s) that associates with NEMO, likely by linking NEMO to TRAF6. Consistently, we found TRAF6 deficiency also abrogates GPCR-induced NF-κB activation. Together, our results provide the genetic evidence that CARMA3 is required for GPCR-induced NF-κB activation.
Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites
Authors: Parrish Jay Z. , Emoto Kazuo , Jan Lily Yeh , Jan Yuh Nung
Published: April 2007

Dendritic fields are important determinants of neuronal function. However, how neurons establish and then maintain their dendritic fields is not well understood. Here we show that Polycomb group (PcG) genes are required for maintenance of complete and nonoverlapping dendritic coverage of the larval body wall by Drosophila class IV dendrite arborization (da) neurons. In esc, Su(z)12, or Pc mutants, dendritic fields are established normally, but class IV neurons display a gradual loss of dendritic coverage, while axons remain normal in appearance, demonstrating that PcG genes are specifically required for dendrite maintenance. Both multiprotein Polycomb repressor complexes (PRCs) involved in transcriptional silencing are implicated in regulation of dendrite arborization in class IV da neurons, likely through regulation of homeobox (Hox) transcription factors. We further show genetic interactions and association between PcG proteins and the tumor suppressor kinase Warts (Wts), providing evidence for their cooperation in multiple developmental processes including dendrite maintenance.
SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress
Authors: Scher Michael B. , Vaquero Alejandro , Reinberg Danny
Published: April 2007

In humans, there are at least seven Sir2-like proteins (SirT1–7) with diverse functions, including the regulation of chromatin structure, and metabolism. SirT3 levels have been shown to correlate with extended life span, to localize to the mitochondria, and to be highly expressed in brown adipose tissue. In humans, SirT3 exists in two forms, a full-length protein of ∼44 kDa and a processed polypeptide lacking 142 amino acids at its N terminus. We found that SirT3 not only localizes to the mitochondria, but also to the nucleus under normal cell growth conditions. Both the full-length and processed forms of SirT3 target H4-K16 for deacetylation in vitro and can deacetylate H4-K16 in vivo when recruited to a gene. Using a highly specific antibody against the N terminus of SirT3, we found that SirT3 is transported from the nucleus to the mitochondria upon cellular stress. This includes DNA damage induced by Etoposide and UV-irradiation, as well as overexpression of SirT3 itself.
Single-stranded DNA-binding proteins regulate the abundance of LIM domain and LIM domain-binding proteins
Authors: Xu Zhixiong , Meng Xianzhang , Cai Ying , Liang Hong , Nagarajan Lalitha , Brandt Stephen J.
Published: April 2007

The LIM domain-binding protein Ldb1 is an essential cofactor of LIM-homeodomain (LIM-HD) and LIM-only (LMO) proteins in development. The stoichiometry of Ldb1, LIM-HD, and LMO proteins is tightly controlled in the cell and is likely a critical determinant of their biological actions. Single-stranded DNA-binding proteins (SSBPs) were recently shown to interact with Ldb1 and are also important in developmental programs. We establish here that two mammalian SSBPs, SSBP2 and SSBP3, contribute to an erythroid DNA-binding complex that contains the transcription factors Tal1 and GATA-1, the LIM domain protein Lmo2, and Ldb1 and binds a bipartite E-box-GATA DNA sequence motif. In addition, SSBP2 was found to augment transcription of the Protein 4.2 (P4.2) gene, a direct target of the E-box-GATA-binding complex, in an Ldb1-dependent manner and to increase endogenous Ldb1 and Lmo2 protein levels, E-box-GATA DNA-binding activity, and P4.2 and β-globin expression in erythroid progenitors. Finally, SSBP2 was demonstrated to inhibit Ldb1 and Lmo2 interaction with the E3 ubiquitin ligase RLIM, prevent RLIM-mediated Ldb1 ubiquitination, and protect Ldb1 and Lmo2 from proteasomal degradation. These results define a novel biochemical function for SSBPs in regulating the abundance of LIM domain and LIM domain-binding proteins.
Hippo signaling in organ size control
Authors: Pan Duojia
Published: April 2007

The control of organ (or organism) size is a fundamental aspect of life that has long captured human imagination. What makes an elephant grow a million times larger than a mouse? How do our two hands develop independently of each other yet reach very similar size? How does a liver precisely regenerate its original mass when two-thirds of it is removed? The recent discovery of a novel signaling network in Drosophila, known as the Hippo (Hpo) pathway, might provide an important entry point to these fascinating questions. The Hpo pathway consists of several negative growth regulators acting in a kinase cascade that ultimately phosphorylates and inactivates Yorkie (Yki), a transcriptional coactivator that positively regulates cell growth, survival, and proliferation. Components of the Hpo pathway are highly conserved throughout evolution, suggesting that this pathway may function as a global regulator of tissue homeostasis in all metazoan animals. Here, I provide a historical review of this potent growth-regulatory pathway and highlight outstanding questions that will likely be the focus of future investigation.
CHD4/Mi-2β activity is required for the positioning of the mesoderm/neuroectoderm boundary in Xenopus
Authors: Linder Britta , Mentele Edith , Mansperger Katrin , Straub Tobias , Kremmer Elisabeth , Rupp Ralph A.W.
Published: April 2007

Experiments in Xenopus have illustrated the importance of extracellular morphogens for embryonic gene regulation in vertebrates. Much less is known about how induction leads to the correct positioning of boundaries; for example, between germ layers. Here we report that the neuroectoderm/mesoderm boundary is controlled by the chromatin remodeling ATPase CHD4/Mi-2β. Gain and loss of CHD4 function experiments shifted this boundary along the animal–vegetal axis at gastrulation, leading to excess mesoderm formation at the expense of neuroectoderm, or vice versa. This phenotype results from specific alterations in gene transcription, notably of the neural-promoting gene Sip1 and the mesodermal regulatory gene Xbra. We show that CHD4 suppresses Sip1 transcription by direct binding to the 5′ end of the Sip1 gene body. Furthermore, we demonstrate that CHD4 and Sip1 expression levels determine the “ON” threshold for Nodal-dependent but not for eFGF-dependent induction of Xbra transcription. The CHD4/Sip1 epistasis thus constitutes a regulatory module, which balances mesoderm and neuroectoderm formation.
Structural and functional characterization of a novel, host penetration‐related pectate lyase from the potato cyst nematode Globodera rostochiensis
Authors: KUDLA URSZULA , MILAC ADINA‐LUMINITA , QIN LING , OVERMARS HEIN , ROZE ERWIN , HOLTERMAN MARTIJN , PETRESCU ANDREI‐JOSE , GOVERSE ASKA , BAKKER JAAP , HELDER JOHANNES , SMANT GEERT
Published: April 2007

The cell wall, a strong extraprotoplasmic layer surrounding plant cells that mainly consists of a variety of polysaccharides, constitutes a major barrier for potential parasites. Plant‐parasitic nematodes are well equipped to overcome this barrier as they produce and secrete cell‐wall‐degrading enzymes. Expression profiling of various life stages of the potato cyst nematode Globodera rostochiensis revealed a novel pectate lyase gene (Gr‐pel2, 759 bp). The Gr‐PEL2 protein showed highest similarity to pectate lyases from the facultative plant‐parasitic nematodes Bursaphelenchus mucronatus and B. xylophilus and the soil‐inhabiting saprophytic Streptomyces and Frankia species (i.e. 40–42% identity and 58–60% similarity), whereas only a remote relatedness to the previously identified Gr‐PEL1 was observed (i.e. 28% identity and 43% similarity). Transient expression of Gr‐pel2 in leaves of Nicotiana benthamiana resulted in severe malformations of the infiltrated tissues, not relating to maceration and soft rot symptoms. Ca2+ is known to be essential for pectate lyase activity, and the most likely calcium‐binding site was identified in the Gr‐PEL2 protein by combining homology modelling of the three‐dimensional structure, site‐directed mutagenesis and transient expression in leaves. A highly charged cleft in Gr‐PEL2, which is likely to be involved in substrate binding and which is also significantly more hydrophobic in Gr‐PEL1, was shown to be essential for protein activity. Our results underline the broad spectrum of pectate lyases and cell‐wall‐degrading enzymes necessary for successful parasitism by cyst nematodes.
Molecular and cytological responses of Medicago truncatula to Erysiphe pisi
Authors: FOSTER‐HARTNETT DAWN , DANESH DARIUSH , PEÑUELA SILVIA , SHAROPOVA NATASHA , ENDRE GABRIELLA , VANDENBOSCH KATHRYN A. , YOUNG NEVIN D. , SAMAC DEBORAH A.
Published: April 2007

Powdery mildew is an economically important disease in a number of crop legumes; however, little is known about resistance to the disease in these species. To gain a better understanding of the genetics of resistance and plant responses to powdery mildew in legumes, we developed a pathosystem with Medicago truncatula and Erysiphe pisi. Screening accessions of M. truncatula identified genotypes that are highly susceptible, moderately resistant and highly resistant to the fungus. In the highly resistant genotype, fungal growth was arrested after appressorium development with no colony formation, while in the moderately resistant genotype a small number of colonies formed. Both resistant and moderately resistant genotypes produced hydrogen peroxide and fluorescent compounds at pathogen penetration sites, consistent with a hypersensitive response (HR), although the response was delayed in the moderately resistant genotype. Very little hydrogen peroxide or fluorescence was detected in the susceptible accession. Microarray analysis of E. pisi‐induced early transcriptional changes detected 55 genes associated with the basal defence response that were similarly regulated in all three genotypes. These included pathogenesis‐related genes and other genes involved in defence, signal transduction, senescence, cell wall metabolism and abiotic stress. Genes associated with the HR response included flavonoid pathway genes, and others involved in transport, transcription regulation and signal transduction. A total of 34 potentially novel unknown genes, including two legume‐specific genes, were identified in both the basal response and the HR categories. Potential binding sites for two defence‐related transcription regulators, Myb and Whirly, were identified in promoter regions of induced genes, and four novel motifs were found in promoter regions of genes repressed in the resistant interaction.
Very low‐grade metamorphic study in the pre‐Late Cretaceous terranes of New Caledonia (southwest Pacific Ocean)
Authors: Potel Sébastien
Published: April 2007

Abstract  Pre‐Late Cretaceous terranes from the central part of New Caledonia have been metamorphosed under very low‐grade conditions by two high‐pressure/low‐temperature events. The present study investigates the metamorphic patterns with phyllosilicate crystallinities, electron microprobe analyses and petrography. The first metamorphic event is of Late Jurassic age and is characterized by very low (anchizone) to low‐grade (epizone) conditions with a decrease of the illite Kübler Index (KI) and the chlorite Árkai Index (ÁI) values from northeast to southwest. This trend is also confirmed by chlorite thermometry. In the south of the area, un‐metamorphosed sediments (diagenetic KI values) are observed in the Senonian ‘formation à charbons’, post‐dating the metamorphism in this region. The second metamorphism is an Eocene high‐pressure event, which overprints the Late Jurassic metamorphism in the northern part of the studied area. In this zone, the pattern of KI and ÁI indicates another gradient with increasing metamorphic conditions from southwest to northeast. Temperatures calculated by chlorite thermometry also indicate an evolution from southwest to northeast with slight increase of temperature from 298 ± 8°C to 327 ± 16°C. In both metamorphic zones, the K‐white mica b cell dimension calculated on micas analyzed at electron microprobe are in good agreement with high‐pressure/low‐temperature metamorphic conditions (b0 > 9.04 Å). A combination of chlorite thermometry and K‐white mica b cell dimension allows estimation of a minimum pressure of 1.3 GPa in the Eocene zone (in excellent agreement with the 1.5 GPa registered in the northern part of New Caledonia) and a minimum of 1.1 GPa in the Late Jurassic metamorphic part.
The oceanic substratum of Northern Luzon: Evidence from xenoliths within Monglo adakite (the Philippines)
Authors: Payot Betchaida D. , Jego Sebastien , Maury Rene C. , Polve Mireille , Gregoire Michel , Ceuleneer Georges , Tamayo Rodolfo A. , Yumul Graciano P. , Bellon Herve , Cotten Joseph
Published: April 2007

Abstract  A 8.65 Ma adakitic intrusive sheet exposed near Monglo village in the Baguio District of Northern Luzon contains a suite of ultramafic and mafic xenoliths including in order of abundance: spinel dunites showing typical mantle‐related textures, mineral and bulk rock compositions, and serpentinites derived from them; amphibole‐rich gabbros displaying incompatible element patterns similar to those of flat or moderately enriched back‐arc basin basalt magmas; and amphibolites derived from metabasalts and/or metagabbros of identical affinity. A single quartz diorite xenolith carrying a similar subduction‐related geochemical signature has also been sampled. One amphibolite xenolith provided a whole‐rock K–Ar age of 115.6 Ma (Barremian). We attribute the origin of this suite to the sampling by ascending adakitic magmas of a Lower Cretaceous ophiolitic complex located at a depth within the 30–35 km thick Luzon crust. It could represent an equivalent of the Isabela‐Aurora and Pugo‐Lepanto ophiolitic massifs exposed in Northern Luzon.
Correlation between EGFR gene mutation pattern and Akt phosphorylation in pulmonary adenocarcinomas
Authors: Ikeda Satoshi , Takabe Kazuhiko , Inagaki Masaharu , Funakoshi Naoya , Suzuki Keiko , Shibata Toshikatsu
Published: April 2007

The detection of gene mutation of epithelial growth factor receptor (EGFR) is important to predict the therapeutic effect of gefitinib. Recently, it was reported that examination of the activation of the downstream protein of EGFR is useful in the same way as the EGFR mutation. Therefore the purpose of the present paper was to determine whether activation of Akt and Erk, which are downstream proteins, and the EGFR gene mutation pattern was correlated. A total of 130 pulmonary adenocarcinomas were studied for the gene mutations of EGFR in exon 19 and 21, and the phosphorylation of Akt and Erk was investigated by immunostaining. The EGFR mutation was detected in 32%, the positivity of p‐Akt was 51%, and the rate of p‐Erk was 27%. The EGFR mutation‐positive cases were the minority in p‐Akt‐negative cases, and the p‐Akt expression was significantly associated with the mutation of EGFR (P = 0.0014). In addition, there was a significant correlation between the L858R mutation and the expression of p‐Akt (P = 0.040). It is suggested that the activation of Akt is dependent on EGFR mutation pattern.