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111.
112.
Wladimir J. Alonso Maia A. Rabaa Ricardo Giglio Mark A. Miller Cynthia Schuck-Paim 《PloS one》2015,10(10)
Existing modeling approaches are divided between a focus on the constitutive (micro) elements of systems or on higher (macro) organization levels. Micro-level models enable consideration of individual histories and interactions, but can be unstable and subject to cumulative errors. Macro-level models focus on average population properties, but may hide relevant heterogeneity at the micro-scale. We present a framework that integrates both approaches through the use of temporally structured matrices that can take large numbers of variables into account. Matrices are composed of several bidimensional (time×age) grids, each representing a state (e.g. physiological, immunological, socio-demographic). Time and age are primary indices linking grids. These matrices preserve the entire history of all population strata and enable the use of historical events, parameters and states dynamically in the modeling process. This framework is applicable across fields, but particularly suitable to simulate the impact of alternative immunization policies. We demonstrate the framework by examining alternative strategies to accelerate measles elimination in 15 developing countries. The model recaptured long-endorsed policies in measles control, showing that where a single routine measles-containing vaccine is employed with low coverage, any improvement in coverage is more effective than a second dose. It also identified an opportunity to save thousands of lives in India at attractively low costs through the implementation of supplementary immunization campaigns. The flexibility of the approach presented enables estimating the effectiveness of different immunization policies in highly complex contexts involving multiple and historical influences from different hierarchical levels. 相似文献
113.
Harianto Rahardjo Nina Amalia Leong Eng Choon Fakhrur Rozy Harnas Lee Tsen Tieng Fong Yok King 《Landscape and Ecological Engineering》2017,13(1):81-92
The shear strength of soil is an important parameter that affects tree stability and can vary depending on the magnitude of the soil’s negative pore-water pressure (matric suction). The surface flux boundary condition affects the matric suction of soil, and therefore is important for tree stability. Field measurements were performed around a roadside tree for 2 years. The instrumentation results show that the matric suction in the soil fluctuated between 0 and 35 kPa. Matric suction changes in the soil could lead to a decrease in the tree resistive moment of up to 80 %. 相似文献
114.
115.
Monotherapy with a novel intervenolin derivative,AS‐1934, is an effective treatment for Helicobacter pylori infection
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116.
117.
Endah Dwi Hartuti Daniel Ken Inaoka Keisuke Komatsuya Yukiko Miyazaki Russell J. Miller Wang Xinying Mohamad Sadikin Erwahyuni Endang Prabandari Danang Waluyo Marie Kuroda Eri Amalia Yuichi Matsuo Nuki B. Nugroho Hiroyuki Saimoto Amila Pramisandi Yoh-Ichi Watanabe Mihoko Mori Kazuro Shiomi Kiyoshi Kita 《BBA》2018,1859(3):191-200
Plasmodium falciparum is an apicomplexan parasite that causes the most severe malaria in humans. Due to a lack of effective vaccines and emerging of drug resistance parasites, development of drugs with novel mechanisms of action and few side effects are imperative. To this end, ideal drug targets are those essential to parasite viability as well as absent in their mammalian hosts. The mitochondrial electron transport chain (ETC) of P. falciparum is one source of such potential targets because enzymes, such as L-malate:quinone oxidoreductase (PfMQO), in this pathway are absent humans. PfMQO catalyzes the oxidation of L-malate to oxaloacetate and the simultaneous reduction of ubiquinone to ubiquinol. It is a membrane protein, involved in three pathways (ETC, the tricarboxylic acid cycle and the fumarate cycle) and has been shown to be essential for parasite survival, at least, in the intra-erythrocytic asexual stage. These findings indicate that PfMQO would be a valuable drug target for development of antimalarial with novel mechanism of action. Up to this point in time, difficulty in producing active recombinant mitochondrial MQO has hampered biochemical characterization and targeted drug discovery with MQO. Here we report for the first time recombinant PfMQO overexpressed in bacterial membrane and the first biochemical study. Furthermore, about 113 compounds, consisting of ubiquinone binding site inhibitors and antiparasitic agents, were screened resulting in the discovery of ferulenol as a potent PfMQO inhibitor. Finally, ferulenol was shown to inhibit parasite growth and showed strong synergism in combination with atovaquone, a well-described anti-malarial and bc1 complex inhibitor. 相似文献
118.
Brain‐derived neurotrophic factor modulates cholesterol homeostasis and Apolipoprotein E synthesis in human cell models of astrocytes and neurons
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119.
Marcos Hikari Toyama Patrícia Dourado Costa José Camillo Novello Benedito de Oliveira José Roberto Giglio Maria Alice da Cruz-Höfling Sergio Marangoni 《The protein journal》1999,18(3):371-378
MP-III 4R PLA2 was purified from the venom of Bothrops pirajai venom (Bahia's jararacussu) after three chromatographic steps which started with RP-HPLC. The complete amino acid sequence of MP-III 4R PLA2 from Bothrops pirajai was determined by amino acid sequencing of reduced and carboxymethylated MP-III 4R and the isolated peptides from clostripain and protease V8 digestion. MP-III 4R is a D49 PLA2 with 121 amino acid residues and has a molecular weight estimated at 13,800 Da, with 14 half-cysteines. This protein showed moderate PLA2 and anticoagulant activity. This PLA2 does not have a high degree of homology with other bothropic PLA2-like myotoxins (~75%) and nonbothropic myotoxins (~60%). MP-III 4R is a new PLA2, which was isolated using exclusively analytical and preparative HPLC methods. Based on the N-terminal sequence and biological activities, MP-III 4R was identified as similar to piratoxin-III (PrTX-III), which was isolated by conventional chromatography based on molecular exclusion ion exchange chromatography. Clinical manifestations indicate that at the site of toxin injection, there may be pain of variable intensity, because animals continue to lick the limb. No clinical sign indicating general toxicity was noticed. Myotoxicity was observed in gastrocnemius muscle cells after exposure to MP-III 4R, with a high frequency (70%) of affected muscle fibers. 相似文献
120.
Bartacek J Fermoso FG Baldó-Urrutia AM van Hullebusch ED Lens PN 《Journal of industrial microbiology & biotechnology》2008,35(11):1465-1474
The influence of cobalt speciation on the toxicity of cobalt to methylotrophic methanogenesis in anaerobic granular sludge
was investigated. The cobalt speciation was studied with three different media that contained varying concentrations of complexing
ligands [carbonates, phosphates and ethylenediaminetetraacetic acid (EDTA)]. Three fractions (nominal added, dissolved and
free) of cobalt were determined in the liquid media and were correlated with data from batch toxicity experiments. The average
concentration of cobalt that was required for 50% inhibition of methanogenic activity (IC50) for free Co2+ in the three sets of measurements was 13 μmol/L with a standard deviation of 22% and a similarity of 72% between the data
obtained in the three different media for the range of cobalt concentrations investigated. The standard deviation of the IC50 for the other two fractions was much higher, i.e. 85 and 144% for the added cobalt and dissolved cobalt, respectively, and
the similarity was almost 0% for both fractions. Complexation (and precipitation) with EDTA, phosphates and carbonates was
shown to decrease the toxicity of cobalt on methylotrophic methanogenesis. The free cobalt concentration is proposed to be
the key parameter to correlate with cobalt toxicity. Thus, the toxicity of cobalt to granular sludge can be estimated based
on the equilibrium-free cobalt concentration. 相似文献