Coordination Dependence of Hyperfine Fields of 5sp Impurities on Ni Surfaces

We present first-principles calculations of the magnetic hyperfine fields H of 5sp impurities on the (001), (111), and (110) surfaces of Ni. We examine the dependence of H on the coordination number by placing the impurity in the surfaces, on top of them at the adatom positions, and in the bulk. We find a strong coordination dependence of H, different and characteristic for each impurity. The behavior is explained in terms of the on-site s-p hybridization as the symmetry is reduced at the surface. Our results are in agreement with recent experimental findings.Comment: 4 pages, 3 figure

A 24-Week, Randomized, Treat-to-Target Trial Comparing Initiation of Insulin Glargine Once-Daily With Insulin Detemir Twice-Daily in Patients With Type 2 Diabetes Inadequately Controlled on Oral Glucose-Lowering Drugs

OBJECTIVE - To determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C <7% without symptomatic hypoglycemia <= 3.1 mmol/l. RESEARCH DESIGN AND METHODS - In this 24-week trial, 973 insulin-naive type 2 diabetic patients on stable oral glucose-lowering drugs with A1CS. 7.0-10.5% were randomized to glargine once daily or detemir twice daily. Insulin doses were systematically titrated. RESULTS - 27.5 and 25.6% of patients reached the primary outcome with glargine and detemir, respectively, demonstrating the noninferiority of glargine. Improvements in A1C were -1.46 +/- 1.09% for glargine and -1.54 +/- 1.11% for detemir (P = 0.149), with similar proportions of patients achieving A1C <7% (P = 0.254) but more detemir-treated patients reaching A1C <6.5% (P = 0.017). Hypoglycemia risk was similar. Weight gain was higher for glargine (difference: 0.77 kg, P <0.001). Glargine doses were lower than detemir doses: 43.5 +/- 129.0 vs. 76.5 +/- 50.5 units/day (P <0.001). CONCLUSIONS - In insulin-naive type 2 diabetic patients, glargine reached similar control as detemir, with more weight gain, but required significantly lower dose

The impacts of EU accession on the agriculture of the Visegrad Countries

The Visegrad Countries (VC)2 joined the European Union in 2004, which has offered several possibilities and challenges for their agriculture. The aim of the paper is to evaluate the status of the sector in the light of latest available data as well as to identify the factors lying behind different country performances. Results suggest that EU accession has had a diverse impact on the Visegrad Countries’ agriculture and member states capitalised their possibilities in a different manner, due to initial conditions and pre- and post-accession policies

Decreased soluble guanylate cyclase contributes to cardiac dysfunction induced by chronic doxorubicin treatment in mice

Aims: The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity. Results: Doxorubicin administration (20 mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC alpha 1-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGC alpha 1 allele [sGC alpha 1(-/-CM)]). After 12 weeks of doxorubicin administration (2 mg/kg/week IP), left ventricular (LV) systolic dysfunction was greater in sGC alpha 1(-/-CM) than WT mice. To further assess whether reduced sGC activity plays a pathogenic role in doxorubicin-induced cardiotoxicity, we studied a mouse model in which decreased cardiac sGC activity was induced by cardiomyocyte-specific expression of a dominant negative sGC alpha 1 mutant (DNsGC alpha 1) upon doxycycline removal (Tet-off). After 8 weeks of doxorubicin administration, DNsGC alpha 1(tg/+), but not WT, mice displayed LV systolic dysfunction and dilatation. The difference in cardiac function and remodeling between DNsGC alpha 1(tg/+) and WT mice was even more pronounced after 12 weeks of treatment. Further impairment of cardiac function was attenuated when DNsGC alpha 1 gene expression was inhibited (beginning at 8 weeks of doxorubicin treatment) by administering doxycycline. Furthermore, doxorubicin-associated reactive oxygen species generation was higher in sGC alpha 1-deficient than WT hearts. Innovation and Conclusion: These data demonstrate that a reduction in cardiac sGC activity worsens doxorubicin-induced cardiotoxicity in mice and identify sGC as a potential therapeutic target. Various pharmacological sGC agonists are in clinical development or use and may represent a promising approach to limit doxorubicin-associated cardiotoxicity

Characterization of the structure of a low Km, rolipram-sensitive cAMP phosphodiesterase. Mapping of the catalytic domain.

Considerable structural similarities are present in a region of approximately 270 amino acids in most known cyclic nucleotide phosphodiesterase (PDE) sequences, opening the possibility that this region encodes the catalytic domain of the enzyme. To test this hypothesis, the structure of a high affinity cAMP PDE (cAMP-PDE) was analyzed by deletion mutations and site-directed mutagenesis. A ratPDE3 cDNA was mutated using a strategy based on fragment amplification by polymerase chain reaction. The effect of the introduced mutations was determined by expressing wild type and mutated proteins in prokaryotic and eukaryotic cells. The level of expression of the PDE protein was monitored by immunoblot analysis using two specific cAMP-PDE polyclonal antibodies and by measuring the PDE activity. After removal of a 99-amino acid region at the carboxyl terminus flanking the conserved domain, the protein retains its catalytic activity even though its Km and velocity were changed. Internal deletions at the amino terminus of this PDE showed that the enzyme activity was increased when a 97-amino acid fragment (from Tyr49 to Lys145) was removed. Further deletions within the amino terminus produced inactive proteins. Within the domain that appears essential for catalysis, 1 threonine and 2 serine residues are conserved in all PDEs. Substitutions of the invariant threonine (Thr349) present in the most conserved region with alanine, proline, or serine yielded proteins of the correct size and a level of expression comparable to the wild type PDE. However, in both expression systems used, proteins were completely devoid of the ability to hydrolyze cyclic nucleotides, except when the threonine was substituted with a serine. Conversely, mutations of 2 other conserved serine residues (Ser305 and Ser398) present in the catalytic domain either had no effect or produced changes only in Km and Vmax, but did not abolish catalytic activity. In addition, 2 histidine residues (His278 and His311) present in proximity to Thr349 appeared to be essential for the structure of the catalytic domain, since any substitution performed in these residues yielded an inactive enzyme. Mutations of a serine residue (Ser295) in the region homologous to the cAMP binding site of the regulatory subunit of the cAMP-dependent protein kinase demonstrated that this region does not have the same function in the two proteins. These data provide direct evidence that a 37-kDa domain, which in part corresponds to the region of conservation in all PDEs, contains the catalytic domain, and that threonine and histidine residues are probably involved in catalysis and/or are essential for the conformation of an active enzyme

Production potential in the "bread baskets" of Eastern Europe and Central Asia

© 2017 Elsevier B.V.Eastern Europe and Central Asia is a major food producer and exporter. Almost a quarter of world wheat exports come from the region, and especially from Kazakhstan, Russia and Ukraine (RUK). The potential of these countries to become a "bread basket" for the world has been emphasized because of already large production and exports and their "immense land and yield reserves", referring to the abandonment of more than 50 million hectares of cropland and the large drop in crop productivity in the 1990s. However, there is considerable uncertainty about the potential of this land for food production. In this paper we review interdisciplinary literature and empirical evidence, predictions of production potential and impacts of climate change; and discuss the potential of the region to become a reliable breadbasket of the world. From a biophysical (crop growth) perspective, under different scenarios of increased yields, land use and climate change effects, RUK could produce an additional 40-110 million tons of wheat compared to current production, which would be a substantial additional production. However economic incentives, in particular the evolution of food prices and competition from other crops, are likely to significantly constrain these potentials. In addition, the introduction of export restrictions during recent times of high prices raised concerns on the reliability of RUK as exporters

Report on the IDRC 2012 Canadian Learning Forum : Virtual Platforms, Knowledge Management and International Development, February 7-8, 2012, Winnipeg

French version available in IDRC Digital Library: Rapport sur le Forum canadien d'apprentissage du CRDI 2012 : plateformes virtuelles, gestion des connaissances et développement international, Winnipeg, les 7 et 8 février 2012Over the past five years, the Canadian Partnerships (CP) program at IDRC has supported a number of Canadian academic, research and civil society organizations to use online virtual platforms (VPs) in their research, policy development, project collaboration, capacity building and dissemination activities. VPs are online tools and systems that are designed to facilitate knowledge sharing, management and collaboration amongst geographically dispersed actors. International development organizations increasingly see these VPs as a means to connecting far-flung staff, partners, participants and supporters to document, compile and make sense of their collective learning to enhance real-world, “off-line results”. Moreover, for organizations that work globally, VPs also offer the advantage of reducing the costs, inconvenience and pollution associated with international travel; and as more and more people in the global South are connecting to the Internet via mobile phones, the potential to reach new constituencies and to support collaboration between local, national and international actors is exciting, but also potentially overwhelming for staff charged with starting up and facilitating the use of these platforms..

Production potential in the “bread baskets” of Eastern Europe and Central Asia

© 2017 Elsevier B.V. Eastern Europe and Central Asia is a major food producer and exporter. Almost a quarter of world wheat exports come from the region, and especially from Kazakhstan, Russia and Ukraine (RUK). The potential of these countries to become a “bread basket” for the world has been emphasized because of already large production and exports and their “immense land and yield reserves”, referring to the abandonment of more than 50 million hectares of cropland and the large drop in crop productivity in the 1990s. However, there is considerable uncertainty about the potential of this land for food production. In this paper we review interdisciplinary literature and empirical evidence, predictions of production potential and impacts of climate change; and discuss the potential of the region to become a reliable breadbasket of the world. From a biophysical (crop growth) perspective, under different scenarios of increased yields, land use and climate change effects, RUK could produce an additional 40–110 million tons of wheat compared to current production, which would be a substantial additional production. However economic incentives, in particular the evolution of food prices and competition from other crops, are likely to significantly constrain these potentials. In addition, the introduction of export restrictions during recent times of high prices raised concerns on the reliability of RUK as exporters

Food Price Shocks and the Political Economy of Global Agricultural and Development Policy

The recent spikes of global food prices induced a rapid increase in mass media coverage, public policy attention, and donor funding for food security and for agriculture and rural poverty. This has occurred while the shift from low to high food prices has induced a shift in (demographic or social) location of the hunger and poverty effects, but the total number of undernourished and poor people has declined over the same period. We suggest that the observed pattern can be explained by the presence of a global urban bias on agriculture and food policy in developing countries, and we discuss whether this global urban bias may actually benefit poor farmers. We argue that the food price spikes have succeeded where others have failed in the past: to move the problems of poor and hungry farmers to the top of the policy agenda and to induce development and donor strategies to help them