Antiamoebic Properties of the Actinomycete Metabolites Echinomycin A and Tirandamycin A

Entamoeba histolytica infects 50 million people per year, causing 100,000 deaths worldwide. The primary treatment for amoebiasis is metronidazole. However, increased pathogen resistance combined with the drug’s toxic side effects encourages a search for alternative therapeutic agents. Secondary metabolites from marine bacteria are a promising resource for antiprotozoan drug discovery. In this study, extracts from a collection of marine-derived actinomycetes were screened for antiamoebic properties, and the activities of antibiotics echinomycin A and tirandamycin A are shown. Both antibiotics inhibited the in vitro growth of a E. histolytica laboratory strain (HM-1:IMSS) and a clinical isolate (Colombia, Col) at 30- to 60-μM concentrations. EIC50 (estimated inhibitory concentration) values were comparable for both antibiotics (44.3–46.3 μM) against the E. histolytica clinical isolate

Density Matrix Renormalization for Model Reduction in Nonlinear Dynamics

We present a novel approach for model reduction of nonlinear dynamical systems based on proper orthogonal decomposition (POD). Our method, derived from Density Matrix Renormalization Group (DMRG), provides a significant reduction in computational effort for the calculation of the reduced system, compared to a POD. The efficiency of the algorithm is tested on the one dimensional Burgers equations and a one dimensional equation of the Fisher type as nonlinear model systems.Comment: 12 pages, 12 figure

Fusion barrier distributions in systems with finite excitation energy

Eigen-channel approach to heavy-ion fusion reactions is exact only when the excitation energy of the intrinsic motion is zero. In order to take into account effects of finite excitation energy, we introduce an energy dependence to weight factors in the eigen-channel approximation. Using two channel problem, we show that the weight factors are slowly changing functions of incident energy. This suggests that the concept of the fusion barrier distribution still holds to a good approximation even when the excitation energy of the intrinsic motion is finite. A transition to the adiabatic tunneling, where the coupling leads to a static potential renormalization, is also discussed.Comment: 9 pages, 4 figures, Submitted to Physical Review

Calcium-mediated stabilisation of soil organic carbon

Soils play an essential role in the global cycling of carbon and understanding the stabilisation mechanisms behind the preservation of soil organic carbon (SOC) pools is of globally recognised significance. Until recently, research into SOC stabilisation has predominantly focused on acidic soil environments and the interactions between SOC and aluminium (Al) or iron (Fe). The interactions between SOC and calcium (Ca) have typically received less attention, with fewer studies conducted in alkaline soils. Although it has widely been established that exchangeable Ca (CaExch) positively correlates with SOC concentration and its resistance to oxidation, the exact mechanisms behind this relationship remain largely unidentified. This synthesis paper critically assesses available evidence on the potential role of Ca in the stabilisation of SOC and identifies research topics that warrant further investigation. Contrary to the common view of the chemistry of base cations in soils, chemical modelling indicates that Ca2+ can readily exchange its hydration shell and create inner sphere complexes with organic functional groups. This review therefore argues that both inner- and outer-sphere bridging by Ca2+ can play an active role in the stabilisation of SOC. Calcium carbonate (CaCO3) can influence occluded SOC stability through its role in the stabilisation of aggregates; however, it could also play an unaccounted role in the direct sorption and inclusion of SOC. Finally, this review highlights the importance of pH as a potential predictor of SOC stabilisation mechanisms mediated by Al- or Fe- to Ca, and their respective effects on SOC dynamics

Grid Loss: Detecting Occluded Faces

Detection of partially occluded objects is a challenging computer vision problem. Standard Convolutional Neural Network (CNN) detectors fail if parts of the detection window are occluded, since not every sub-part of the window is discriminative on its own. To address this issue, we propose a novel loss layer for CNNs, named grid loss, which minimizes the error rate on sub-blocks of a convolution layer independently rather than over the whole feature map. This results in parts being more discriminative on their own, enabling the detector to recover if the detection window is partially occluded. By mapping our loss layer back to a regular fully connected layer, no additional computational cost is incurred at runtime compared to standard CNNs. We demonstrate our method for face detection on several public face detection benchmarks and show that our method outperforms regular CNNs, is suitable for realtime applications and achieves state-of-the-art performance.Comment: accepted to ECCV 201

Dose escalation of desmoteplase for acute ischemic stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset

<p><b>Background and Purpose:</b> Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.</p> <p><b>Methods:</b> DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 μg/kg and 125 μg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.</p> <p><b>Results:</b> Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 μg/kg: n=14; 125 μg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 μg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 μg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 μg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 μg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 μg/kg desmoteplase (P=0.022).</p> <p><b>Conclusions:</b> Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 μg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).</p&gt

RNA-Containing Cytoplasmic Inclusion Bodies in Ciliated Bronchial Epithelium Months to Years after Acute Kawasaki Disease

Kawasaki Disease (KD) is the most common cause of acquired heart disease in children in developed nations. The KD etiologic agent is unknown but likely to be a ubiquitous microbe that usually causes asymptomatic childhood infection, resulting in KD only in genetically susceptible individuals. KD synthetic antibodies made from prevalent IgA gene sequences in KD arterial tissue detect intracytoplasmic inclusion bodies (ICI) resembling viral ICI in acute KD but not control infant ciliated bronchial epithelium. The prevalence of ICI in late-stage KD fatalities and in older individuals with non-KD illness should be low, unless persistent infection is common.Lung tissue from late-stage KD fatalities and non-infant controls was examined by light microscopy for the presence of ICI. Nucleic acid stains and transmission electron microscopy (TEM) were performed on tissues that were strongly positive for ICI. ICI were present in ciliated bronchial epithelium in 6/7 (86%) late-stage KD fatalities and 7/27 (26%) controls ages 9-84 years (p = 0.01). Nucleic acid stains revealed RNA but not DNA within the ICI. ICI were also identified in lung macrophages in some KD cases. TEM of bronchial epithelium and macrophages from KD cases revealed finely granular homogeneous ICI.These findings are consistent with a previously unidentified, ubiquitous RNA virus that forms ICI and can result in persistent infection in bronchial epithelium and macrophages as the etiologic agent of KD

Japanese multinationals in the post-bubble era:new challenges and evolving capabilities

Since the bursting of Japan's bubble economy, from 1990 onwards, Japanese multinational companies (MNCs) have faced new competitive challenges and questions about the management practices on which they had built their initial success in global markets. Japanese engagement in the international economy has undergone a number of phases. In the period before the Second World War, Japanese companies learnt from foreign MNCs in trading, shipping, and manufacturing, frequently through strategic alliances, and leveraged their capabilities to succeed in overseas and largely Asian markets. In the immediate post-war decades, during the Japanese ‘economic miracle’, there were notable examples of MNC investment in raw materials and labour intensive production, but both inward and outward foreign direct investment were not significant. Japanese companies achieved leadership in management and technology, in order to support a strategy of export-orientated industrialization. Changes in government policies in the developed economies of the US and Western Europe forced leading Japanese manufacturers to convert themselves into MNCs and to transfer their home-grown capabilities to overseas subsidiaries. The period after 1990 marked declining Japanese competitiveness and it asked questions about the ability of Japanese MNCs to be more responsive and global in their strategies, organization and capabilities.No Full Tex