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21.
Background
The way we formulate a mathematical model of an infectious disease to capture symptomatic and asymptomatic transmission can greatly influence the likely effectiveness of vaccination in the presence of vaccine effect for preventing clinical illness. The present study aims to assess the impact of model building strategy on the epidemic threshold under vaccination.Methodology/Principal Findings
We consider two different types of mathematical models, one based on observable variables including symptom onset and recovery from clinical illness (hereafter, the “observable model”) and the other based on unobservable information of infection event and infectiousness (the “unobservable model”). By imposing a number of modifying assumptions to the observable model, we let it mimic the unobservable model, identifying that the two models are fully consistent only when the incubation period is identical to the latent period and when there is no pre-symptomatic transmission. We also computed the reproduction numbers with and without vaccination, demonstrating that the data generating process of vaccine-induced reduction in symptomatic illness is consistent with the observable model only and examining how the effective reproduction number is differently calculated by two models.Conclusions
To explicitly incorporate the vaccine effect in reducing the risk of symptomatic illness into the model, it is fruitful to employ a model that directly accounts for disease progression. More modeling studies based on observable epidemiological information are called for. 相似文献22.
Holliday junction (HJ) resolvases are structure-specific endonucleases that cleave four-way DNA junctions (HJs) generated during DNA recombination and repair. Bacterial RuvC, a prototypical HJ resolvase, functions as homodimer and nicks DNA strands precisely across the junction point. To gain insights into the mechanisms underlying symmetrical strand cleavages by RuvC, we performed crystallographic and biochemical analyses of RuvC from Thermus thermophilus (T.th. RuvC). The crystal structure of T.th. RuvC shows an overall protein fold similar to that of Escherichia coli RuvC, but T.th. RuvC has a more tightly associated dimer interface possibly reflecting its thermostability. The binding mode of a HJ-DNA substrate can be inferred from the shape/charge complementarity between the T.th. RuvC dimer and HJ-DNA, as well as positions of sulfate ions bound on the protein surface. Unexpectedly, the structure of T.th. RuvC homodimer refined at 1.28 Å resolution shows distinct asymmetry near the dimer interface, in the region harboring catalytically important aromatic residues. The observation suggests that the T.th. RuvC homodimer interconverts between two asymmetric conformations, with alternating subunits switched on for DNA strand cleavage. This model provides a structural basis for the ‘nick-counter-nick’ mechanism in HJ resolution, a mode of HJ processing shared by prokaryotic and eukaryotic HJ resolvases. 相似文献
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Keisuke Ueda Chieko Kimura-Sakiyama Tomoki Aihara Masao Miki Toshiaki Arata 《Biophysical journal》2013
To identify the interaction sites of Tm, we measured the rotational motion of a spin-label covalently bound to the side chain of a cysteine that was genetically incorporated into rabbit skeletal muscle tropomyosin (Tm) at positions 13, 36, 146, 160, 174, 190, 209, 230, 271, or 279. Most of the Tm residues were immobilized on actin filaments with myosin-S1 bound to them. The residues in the mid-portion of Tm, namely, 146, 174, 190, 209, and 230, were mobilized when the troponin (Tn) complex bound to the actin-Tm-S1 filaments. The addition of Ca2+ ions partially reversed the Tn-induced mobilization. In contrast, residues at the joint region of Tm, 13, 36, 271, and 279 were unchanged or oppositely changed. All of these changes were detected using a maleimide spin label and less obviously using a methanesulfonate label. These results indicated that Tm was fixed on thin filaments with myosin bound to them, although a small change in the flexibility of the side chains of Tm residues, presumably interfaced with Tn, actin and myosin, was induced by the binding of Tn and Ca2+. These findings suggest that even in the myosin-bound (open) state, Ca2+ may regulate actomyosin contractile properties via Tm. 相似文献
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Yusuke Tani Keisuke Araki Takehiro Nagai Kowa Koida Shigeki Nakauchi Michiteru Kitazaki 《PloS one》2013,8(1)
It has been argued that when an observer moves, a contingent retinal-image motion of a stimulus would strengthen the perceived glossiness. This would be attributed to the veridical perception of three-dimensional structure by motion parallax. However, it has not been investigated whether the effect of motion parallax is more than that of retinal-image motion of the stimulus. Using a magnitude estimation method, we examine in this paper whether cross-modal coordination of the stimulus change and the observer''s motion (i.e., motion parallax) is essential or the retinal-image motion alone is sufficient for enhancing the perceived glossiness. Our data show that a retinal-image motion simulating motion parallax without head motion strengthened the perceived glossiness but that its effect was weaker than that of motion parallax with head motion. These results suggest the existence of an additional effect of the cross-modal coordination between vision and proprioception on glossiness perception. That is, motion parallax enhances the perception of glossiness, in addition to retinal-image motions of specular surfaces. 相似文献
27.
Hirotsugu Ohkubo Yoshihiro Kanemitsu Takehiro Uemura Osamu Takakuwa Masaya Takemura Ken Maeno Yutaka Ito Tetsuya Oguri Nobutaka Kazawa Ryuji Mikami Akio Niimi 《PloS one》2016,11(3)
BackgroundAlthough several computer-aided computed tomography (CT) analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF), it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF.ObjectiveThe purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF.MethodsA total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR) CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology) staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT), the normally attenuated lung volume as defined from −950 HU to −701 Hounsfield unit (NL), the volume of the whole lung (WL), and the percentage of NL to WL (NL%), were calculated.ResultsCT indices (MCT, WL, and NL) closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC) (r = 0.92, P <0.0001). NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI), 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05]).ConclusionThe measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging. 相似文献
28.
Chiung-Kuei Huang Yoshifumi Iwagami Arihiro Aihara Waihong Chung Suzanne de la Monte John-Michael Thomas Mark Olsen Rolf Carlson Tunan Yu Xiaoqun Dong Jack Wands 《PloS one》2016,11(3)
Cholangiocarcinoma (CCA) has a poor prognosis due to widespread intrahepatic spread. Aspartate β-hydroxylase (ASPH) is a transmembrane protein and catalyzes the hydroxylation of aspartyl and asparaginyl residues in calcium binding epidermal growth factor (cbEGF)-like domains of various proteins, including Notch receptors and ligands. ASPH is highly overexpressed (>95%) in human CCA tumors. We explored the molecular mechanisms by which ASPH mediated the CCA malignant phenotype and evaluated the potential of ASPH as a therapeutic target for CCA. The importance of expression and enzymatic activity of ASPH for CCA growth and progression was examined using shRNA “knockdown” and a mutant construct that reduced its catalytic activity. Second generation small molecule inhibitors (SMIs) of β-hydroxylase activity were developed and used to target ASPH in vitro and in vivo. Subcutaneous and intrahepatic xenograft rodent models were employed to determine anti-tumor effects on CCA growth and development. It was found that the enzymatic activity of ASPH was critical for mediating CCA progression, as well as inhibiting apoptosis. Mechanistically, ASPH overexpression promoted Notch activation and modulated CCA progression through a Notch1-dependent cyclin D1 pathway. Targeting ASPH with shRNAs or a SMI significantly suppressed CCA growth in vivo. 相似文献
29.
Background and aim
Recycled sources of phosphorus (P), such as struvite extracted from wastewater, have potential to substitute for more soluble manufactured fertilisers and help reduce the long-term threat to food security from dwindling finite reserves of phosphate rock (PR). This study aimed to determine whether struvite could be a component of a sustainable P fertiliser management strategy for arable crops.Methods
A combination of laboratory experiments, pot trials and mathematical modelling of the root system examined the P release properties of commercial fertiliser-grade struvite and patterns of P uptake from a low-P sandy soil by two different crop types, in comparison to more soluble inorganic P fertilisers (di-ammonium phosphate (DAP) and triple super phosphate (TSP)).Results
Struvite had greatly enhanced solubility in the presence of organic acid anions; buckwheat, which exudes a high level of organic acids, was more effective at mobilising struvite P than the low level exuder, spring wheat. Struvite granules placed with the seed did not provide the same rate of P supply as placed DAP granules for early growth of spring wheat, but gave equivalent rates of P uptake, yield and apparent fertiliser recovery at harvest, even though only 26 % of struvite granules completely dissolved. Fertiliser mixes containing struvite and DAP applied to spring wheat have potential to provide both optimal early and late season P uptake and improve overall P use efficiency.Conclusions
We conclude that the potential resource savings and potential efficiency benefits of utilising a recycled slow release fertiliser like struvite offers a more sustainable alternative to only using conventional, high solubility, PR-based fertilisers.30.
Larval dispersal dampens population fluctuation and shapes the interspecific spatial distribution patterns of rocky intertidal gastropods 下载免费PDF全文
Ryosuke Sahara Keiichi Fukaya Takehiro Okuda Masakazu Hori Tomoko Yamamoto Masahiro Nakaoka Takashi Noda 《Ecography》2016,39(5):487-495
Many marine benthic invertebrates pass through a planktonic larval stage whereas others spend their entire lifetimes in benthic habitats. Recent studies indicate that non‐planktonic species show relatively greater fine‐scale patchiness than do planktonic species, but the underlying mechanisms remain unknown. One hypothesis for such a difference is that larval dispersal enhances the connectivity of populations and buffers population fluctuations and reduces local extinction risk, consequently increasing patch occupancy rate and decreasing spatial patchiness. If this mechanism does indeed play a significant role, then the distribution of non‐planktonic species should be more aggregated – both temporally and spatially – than the distribution of species with a planktonic larval stage. To test this prediction, we compared 1) both the spatial and the temporal abundance–occupancy relationships and 2) both the spatial and the temporal mean–variance relationships of population size across species of rocky intertidal gastropods with differing dispersive traits from the Pacific coast of Japan. We found that, compared to planktonic species, non‐planktonic species exhibited 1) a smaller occupancy rate for any given level of mean population size and 2) greater variations in population size, both spatially and temporally. This suggests that the macroecological patterns observed in this study (i.e. the abundance–occupancy relationships and mean–variance relationships of population size across species) were shaped by the effect of larval dispersal dampening population fluctuation, which works over both space and time. While it has been widely assumed that larval dispersal enhances population fluctuations, larval dispersal may in fact enhance the connectively of populations and buffer population fluctuations and reduce local extinction risks. 相似文献