bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss
Authors: Hoffmann Jennifer , Alt Alex , Lin Jihong , Lochnit Günther , Schubert Uwe , Schleicher Erwin , Chavakis Triantaphyllos , Brownlee Michael , Van der Woude Fokko , Preissner Klaus , Hammes Hans-Peter 
Published: March 2006

SummaryHyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(±)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range anda transition metal ion chelator in the micromolar range. We tested its effect on experimental diabetic retinopathy, and on endothelial cell characteristics in vitro. Streptozotocin diabetic male Wistar rats (60 mg/ kg BW) received 50 mg/kg BW tenilsetam (D-T) for 36 weeks, or no treatment (D).The impact of tenilsetam (0–30 mM) on endothelial proliferation, apoptosis, sprouting, cytokine-induced leucocyte-endothelial interaction, and VEGF expression was tested in vitro.Tenilsetam did not affect glycemic control or body weight in diabetic animals. The 3.7 fold increase in acellular capillaries in diabetic rats [p<0.001 vs. non-diabetic controls (N)] was reduced by 70% (p<0.001) through treatment, but pericyte loss (D vs. N –33%; p<0.001) remained unaffected. In vitro, tenilsetam inhibited endothelial proliferation at lower doses, while inducing apoptosis at high doses. Leucocyte adhesion was only inhibited at high doses. Sprouting angiogenesis of bovine retinal endothelial cells was promoted at lower doses (≤ 10 mM). At micromolar concentrations, endothelial VEGF expression was upregulated by 100%. Long-term treatment with the AGEinhibitor and iron-chelating compound tenilsetam inhibits the formation of acellular capillaries without correcting pericyte loss. The compound has dose-dependent effects on endothelial cell function. These data suggest that, independent of known properties, tenilsetam shows important rescue functions on endothelial cells which could be useful for the treatment of early diabetic retinopathy.
Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism
Authors: Le Gal Grégoire , De Lucia Sylvain , Roy Pierre-Marie , Meyer Guy , Aujesky Drahomir , Bounameaux Henri , Perrier Arnaud , Righini Marc 
Published: March 2006

SummaryLimited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE).Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients witha malignancy. At cut-off values varying from 500 to 900 µg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI:11% to 24%) to 30% (95% CI:22% to 39%).The 3-month thromboembolic risk was 0% (95 % CI: 0% to 18%) in cancer patients witha negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test’s clinical usefulness.
Interleukin-4 differentially regulates osteoprotegerin expression and induces calcification in vascular smooth muscle cells
Authors: Schrader Jörg , Niebergall Ute , Viereck Volker , Burchert Andreas , Hörsch Dieter , Preissner Klaus , Schoppet Michael , Hofbauer Lorenz 
Published: March 2006

SummaryVascular calcification is characterized by cellular transdifferentiation and expression of bone-related matrix proteins that result in the presence of bone-like structures in the vascular wall. Interleukin (IL)-4, a pleiotropic cytokine, and osteoprotegerin (OPG), an essential regulator of osteoclast biology, have both been linked to vascular disease. Here, we assessed the role of IL-4 and OPG in vascular calcification in vitro. IL-4 induced OPG mRNA levels and protein secretion by 5-fold in a dose-and time-dependent fashion in human coronary artery smooth muscle cells (CASMC). Activation of the transcription factor STAT6 preceded IL-4-induced OPG expression, and blockade of IL-4-induced STAT6 activation by the phospholipase C inhibitor D609 decreased OPG expression. Long-term exposure of IL-4 for 4 weeks resulted in transformation of CASMC towards an osteoblastic phenotype, based on the expression of the transcription factor Cbfa1 and increased mineral deposition. Notably, calcification of CASMC was inhibited by gene silencing of Cbfa1. During osteogenic transformation, IL-4 down-regulated OPG production in CASMC. IL-4 has differential effects in CASMC: While short-term exposure enhances OPG production through a STAT6-dependent mechanism, long-term exposure causes Cbfa1-dependent osteogenic transformation anda decreased production of OPG, an inhibitor of bone resorption.
Towards a European Foreign Policy
Authors: Crowe Brian 
Published: March 2006

AbstractThe Balkans have been the crucible of the EU's Common Foreign and Security Policy (CFSP). In the 1990s the appointment of David (Lord) Owen as a strong representative to manage the EU's Bosnian policy, the sidelining of the EU itself by the Contact Group, and American dominance at Dayton (what price 'this is the hour of Europe'?) and over Kosovo were important precursors to the important European Council decisions in June 1999 to appoint a high-profile international statesman as High Representative for the CFSP and to create the EU's own military capability in European Security and Defence Policy (ESDP). The Constitutional Treaty's further provisions, notably replacing the Presidency in external relations, will be sorely missed and will need to be brought back.ESDP is developing well, if modestly, and making a genuine contribution, mostly with a strong civ-mil component, in several parts of the world. The CFSP itself seems to be managing quite well. But the EU is not yet set up for serious 'events' or crisis management. Experience shows, and greater recognition is needed, that the EU (probably even with an EU Foreign Minister) needs to be represented by member states that carry conviction to outside interlocutors: some member states are inevitably more equal and carry greater weight than others, even if all have an equal voice. Since EU foreign policy is in large measure inescapably a function of US foreign policy, member states need to have a better common understanding among themselves about the nature of the transatlantic relationship. It will take confidence in the efficacy of the CFSP, to which all must give greater priority, before those member states that have alternatives will accept being bound to conducting their foreign policy (or being represented in the UN Security Council) through Brussels. at will take time and effort.
Singapore's Diplomacy: Vulnerability into Strength
Authors: Rana Kishan S. 
Published: March 2006

AbstractSingapore is a practitioner of focused, innovative diplomacy, constantly in search of the political space for itself that would overcome its sense of vulnerability resulting from its geopolitical location. This has entailed involving other states in its well-being, constantly searching for ways to make itself relevant to the international community, through niche diplomacy and a proactive style.It has been creative in its use of regional diplomacy. It runs a relatively small network of embassies, with strong centralized control through its foreign ministry; it has economized on its scarce resource — skilled manpower — through extensive use of 'non-resident ambassadors'. Poor accountability to publics, attrition of talent and gender inequality are among its few weaknesses. Some, but not all, of its methods are relevant to other small states.
Diplomacy's Possible Futures
Authors: Henrikson Alan K. 
Published: March 2006

AbstractIn an attempt to think beyond the immediate horizon for diplomacy, five possible futures are envisioned. 'Disintermediation' suggests that diplomats, in competition with a dynamic private sector, may need to adopt business methods and use the internet — or be bypassed. 'Europeanization' could largely subordinate bilateral diplomacy within the regional European Union framework, although space might be left for 'public diplomatic' functions. International 'democratization' would accord a larger role to states hitherto excluded from decision-making within multilateral institutions, and also to civil society. 'Thematization' would require a higher degree of flexibility from diplomats as they engage in crusade-like efforts against terrorism, disease and other such threats. 'Americanization' implies the adjustment by diplomats to a world in which 'international relations' are conducted along the lines of US domestic politics, with lobbying and advocacy becoming major activities. The need to win greater public support, if not necessarily to involve the people directly in diplomacy, is evident in all of these 'projective visions'.
The Diplomacy of Proximity and Specialness: Enhancing Canada's Representation in the United States
Authors: Hocking Brian , Lee Donna 
Published: March 2006

AbstractDiplomatic representation, both as a concept and in terms of its structures and processes, does not receive the attention that it deserves. This is surprising given that it forms a central concern for both analysts and practitioners of diplomacy, with the latter confronting multiple challenges in adapting modes of representation to changes in their international and domestic political environments. One facet of this can be identified in responses to factors that have assumed a significant place in the development of diplomacy — namely distance and proximity. To the growth of proximity in both spatial and issue-oriented terms, the challenge of the 'special relationship' is added in specific contexts. Both factors come together in the case of Canada's attempts to manage its policies towards the United States. Here, strategies have moved through distinct phases responding to domestic and international changes. The latest phase, which is associated with substantial rethinking of the role and structure of Foreign Affairs Canada, assumes the form of what has been labelled the Enhanced Representation Initiative (ERI). The ERI is interesting not only in the Canadian-US context, but because it reveals more general problems for governments seeking to manage the pressures of proximity and a growing number of relationships that assume aspects of 'specialness'.
The Impact of Land Cover Change on a Simulated Storm Event in the Sydney Basin
Authors: Gero A. F. , Pitman A. J. 
Published: March 2006

Abstract
The Regional Atmospheric Modeling System (RAMS) was run at a 1-km grid spacing over the Sydney basin in Australia to assess the impact of land cover change on a simulated storm event. The simulated storm used NCEP–NCAR reanalysis data, first with natural (i.e., pre-European settlement in 1788) land cover and then with satellite-derived land cover representing Sydney's current land use pattern. An intense convective storm develops in the model in close proximity to Sydney's dense urban central business district under current land cover. The storm is absent under natural land cover conditions. A detailed investigation of why the change in land cover generates a storm was performed using factorial analysis, which revealed the storm to be sensitive to the presence of agricultural land in the southwest of the domain. This area interacts with the sea breeze and affects the horizontal divergence and moisture convergence—the triggering mechanisms of the storm. The existence of the storm over the dense urban area of Sydney is therefore coincidental. The results herein support efforts to develop parameterization of urban surfaces in high-resolution simulations of Sydney's meteorological environment but also highlight the need to improve the parameterization of other types of land cover change at the periphery of the urban area, given that these types dominate the explanation of the results.
Impact of New Solar Radiation Parameterization in the Eta Model on the Simulation of Summer Climate over South America
Authors: Tarasova T. A. , Fernandez J. P. R. , Pisnichenko I. A. , Marengo J. A. , Ceballos J. C. , Bottino M. J. 
Published: March 2006

AbstractThe regional Eta workstation (WS) model with horizontal resolution of 40 km has been integrated over South America for January 2003. The NCEP–DOE Reanalysis II was used for initial and lateral boundary conditions. The comparison of the model-simulated and satellite-derived values of monthly mean incident solar radiation at the surface demonstrates that the former values are larger by 20%–30% over the entire region. To improve the surface flux representation in the model, a new solar radiation scheme has been implemented in it. An offline comparison of the original and the new radiation schemes with the detailed line-by-line method demonstrates a higher accuracy for the new scheme. With the new scheme, the model-simulated incident solar radiation at the surface is in a better agreement with the satellite-derived data. Nevertheless, a noticeable systematic difference of 10%–20% still remains, probably because of the incorrect description of cloud parameters in the model. The lower incident solar radiation in the new version of the model causes a decrease of near-surface air temperature by 0.1°–1°C and a decrease of precipitation rate by up to 20%–30% over most of the continent. The increase in the simulated incident solar radiation and temperature is found in the region of the South Atlantic convergence zone, which is responsible for the enhanced cloudiness and precipitation in the central and southeastern parts of Brazil during summer. The model results are compared with observational data of meteorological stations, the Global Precipitation Climatology Project (GPCP), and the South American Low-Level Jet Experiment (SALLJEX) and are discussed.
Understanding Precipitation Changes in Iberia in Early Spring: Weather Typing and Storm-Tracking Approaches
Authors: Paredes Daniel , Trigo Ricardo M. , Garcia-Herrera Ricardo , Trigo Isabel Franco 
Published: March 2006

Abstract
March monthly accumulated precipitation in the central and western regions of the Iberian Peninsula presents a clear continuous decline of 50% during the 1960–97 period. A finer analysis using daily data reveals that this trend is exactly confined to the month of March. However, this is merely the most visible aspect of a larger phenomenon over the North Atlantic/European sector. The European precipitation trends in March for the period 1960–2000 show a clear distribution of increasing precipitation in the northern regions (the British Isles and parts of Scandinavia) together with decreasing trends throughout the western Mediterranean Basin.
Relevant circulation changes over the North Atlantic and European sectors explain these precipitation trends. First, a regional Eulerian approach by means of a weather-type (WT) classification shows that the major rainfall contributors in March display significantly decreasing frequencies for the Iberian Peninsula, in contrast to the corresponding “wet” weather types for the U.K./Ireland sector, which display increasing frequencies. Within a larger context, a Lagrangian approach, based on the analysis of storm tracks over Europe and the North Atlantic region, reveals dramatic changes in the location of cyclones in the last four decades that coincide with the corresponding precipitation trends in Europe. The North Atlantic Oscillation is suggested to be the most important large-scale factor controlling both the circulation changes and the precipitation trends over the Euro–Atlantic area in March. Finally, the potential impact of reduced precipitation for rivers and water resources in the Iberian Peninsula is considered.
Using TRMM/TMI to Retrieve Surface Soil Moisture over the Southern United States from 1998 to 2002
Authors: Gao H. , Wood E. F. , Jackson T. J. , Drusch M. , Bindlish R. 
Published: March 2006

Abstract
Passive microwave remote sensing has been recognized as a potential method for measuring soil moisture. Combined with field observations and hydrological modeling brightness temperatures can be used to infer soil moisture states and fluxes in real time at large scales. However, operationally acquiring reliable soil moisture products from satellite observations has been hindered by three limitations: suitable low-frequency passive radiometric sensors that are sensitive to soil moisture and its changes; a retrieval model (parameterization) that provides operational estimates of soil moisture from top-of-atmosphere (TOA) microwave brightness temperature measurements at continental scales; and suitable, large-scale validation datasets. In this paper, soil moisture is retrieved across the southern United States using measurements from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) X-band (10.65 GHz) radiometer with a land surface microwave emission model (LSMEM) developed by the authors. Surface temperatures required for the retrieval algorithm were obtained from the Variable Infiltration Capacity (VIC) hydrological model using North American Land Data Assimilation System (NLDAS) forcing data. Because of the limited information content on soil moisture in the observed brightness temperatures over regions characterized by heavy vegetation, active precipitation, snow, and frozen ground, quality control flags for the retrieved soil moisture are provided. The resulting retrieved soil moisture database will be available through the NASA Goddard Space Flight Center (GSFC) Distributed Active Archive Center (DAAC) at a 1/8° spatial resolution across the southern United States for the 5-yr period of January 1998 through December 2002. Initial comparisons with in situ observations obtained from the Oklahoma Mesonet resulted in seasonal correlation coefficients exceeding 0.7 for half of the time covered by the dataset. The dynamic range of the satellite-derived soil moisture dataset is considerably higher compared to the in situ data. The spatial pattern of the TMI soil moisture product is consistent with the corresponding precipitation fields.
Probabilistic Quantitative Precipitation Estimation in Complex Terrain
Authors: Clark Martyn P. , Slater Andrew G. 
Published: March 2006

AbstractThis paper describes a flexible method to generate ensemble gridded fields of precipitation in complex terrain. The method is based on locally weighted regression, in which spatial attributes from station locations are used as explanatory variables to predict spatial variability in precipitation. For each time step, regression models are used to estimate the conditional cumulative distribution function (cdf) of precipitation at each grid cell (conditional on daily precipitation totals from a sparse station network), and ensembles are generated by using realizations from correlated random fields to extract values from the gridded precipitation cdfs. Daily high-resolution precipitation ensembles are generated for a 300 km × 300 km section of western Colorado (dx = 2 km) for the period 1980–2003. The ensemble precipitation grids reproduce the climatological precipitation gradients and observed spatial correlation structure. Probabilistic verification shows that the precipitation estimates are reliable, in the sense that there is close agreement between the frequency of occurrence of specific precipitation events in different probability categories and the probability that is estimated from the ensemble. The probabilistic estimates have good discrimination in the sense that the estimated probabilities differ significantly between cases when specific precipitation events occur and when they do not. The method may be improved by merging the gauge-based precipitation ensembles with remotely sensed precipitation estimates from ground-based radar and satellites, or with precipitation and wind fields from numerical weather prediction models. The stochastic modeling framework developed in this study is flexible and can easily accommodate additional modifications and improvements.
The Relationship between Intermodel Differences and Surface Energy Balance Complexity in the Rhône-Aggregation Intercomparison Project
Authors: Fox S. , Pitman A. J. , Boone A. , Habets F. 
Published: March 2006

Abstract
Six modes of complexity of the Chameleon land surface model (CHASM) are used to explore the relationship between the complexity of the surface energy balance (SEB) formulation and the capacity of the model to explain intermodel variations in results from the Rhône-Aggregation Intercomparison Project (Rhône-AGG). At an annual time scale, differences between models identified in the Rhône-AGG experiments in the partitioning of available energy and water at the spatial scale of the Rhône Basin can be reproduced by CHASM via variations in the SEB complexity. Only two changes in the SEB complexity in the model generate statistically significant differences in the mean latent heat flux. These are the addition of a constant surface resistance to the simplest mode of CHASM and the addition of tiling and temporally and spatially variable surface resistance to produce the most complex model. Further, the only statistically significant differences in runoff occur following the addition of a constant surface resistance to the simplest mode of CHASM. As the time scale is reduced from annual to monthly, specific mechanisms begin to dominate the simulations produced by each Rhône-AGG model and introduce parameterization-specific behavior that depends on the time evolution of processes operating on longer time scales. CHASM cannot capture all this behavior by varying the SEB complexity, demonstrating the contribution to intermodel differences by hydrology and snow-related processes. Despite the increasing role of hydrology and snow in simulating processes at finer time scales, provided the constant surface resistance is included, CHASM's modes perform within the range of uncertainty illustrated by other Rhône-AGG models on seasonal and annual time scales.