Anaplasma phagocytophilum, an obligate intracellular bacterium that propagates within host granulocytes, is considered to modify the host intracellular environment for pathogenesis. However, the mechanism(s) underlying such host modifications remain unclear. Here, we aimed to investigate the relation between A. phagocytophilum and endoplasmic reticulum (ER) stress in THP-1 cells. A. phagocytophilum activated the three ER stress sensors: inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor-6 (ATF6). IRE1 activation occurred immediately after host cell invasion by A. phagocytophilum; however, the activated IRE1-induced splicing of X-box-binding protein 1 was not promoted during A. phagocytophilum infection. This suppression was sustained even after the doxycycline-mediated elimination of intracellular A. phagocytophilum. IRE1 knockdown accelerated A. phagocytophilum-induced apoptosis and decreased intracellular A. phagocytophilum. These data suggest that A. phagocytophilum utilizes IRE1 activation to promote its own intracellular proliferation. Moreover, PERK and ATF6 partially mediated A. phagocytophilum-induced apoptosis by promoting the expression of CCAAT/ enhancer-binding protein homologous protein, which induces the transcription of several proapoptotic genes. Thus, A. phagocytophilum possibly manipulates the host ER stress signals to facilitate intracellular proliferation and infection of surrounding cells before/after host cell apoptosis.Abbreviations: ATF4, activating transcription factor-4; ATF6, activating transcription factor-6; Ats-1, Anaplasma translocated substrate-1; BCL-2, B-cell lymphoma 2; cDNA, complementary DNA; CHOP, CCAAT/enhancer-binding protein homologous protein; DC, dense-cored cells; eIF2α, eukaryotic translation initiation factor-2 α subunit; ER, endoplasmic reticulum; ESAT-6, early secreted antigenic target of 6 kDa; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IRE1, inositol-requiring enzyme-1; Msp2, major surface protein 2; PARP, poly(ADP-ribose) polymerase; PERK, protein kinase RNA-like endoplasmic reticulum kinase; pi, postinfection; p-IRE1, phosphorylated-inositol-requiring enzyme-1; p-PERK, phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase; RC, reticulate cells; RT-qPCR, reverse transcription real-time PCR; siRNA, small interfering RNA; T4SS, type IV secretion system; UPR, unfolded protein response; VacA, vacuolating cytotoxin A; XBP1s, spliced form of X-boxbinding protein 1; XBP1, X-box-binding protein 1.
In this study, the authors have developed the simple and accurate formulae of the Froude-Krylov forces of 6-DOFs based on the linear theory, as a fundamental study to develop a closed formula of ship motion in waves. The proposed formulae have been developed by approximating the hull-form under waterline by the function uniquely determined by the principal particulars of the ship; length L, breadth B, draft d, block coefficient Cb, waterplane area coefficient Cw, midship section area coefficient Cm, height of center of gravity KG, longitudinal center of floatation LCF. Therefore, the proposed formulae are expressed as the explicit function determined by only principal particulars as well as the wave condition parameters. It was confirmed that the proposed formulae have high accuracy for all merchant ship types in any wave condition (wave angle and wave length) through validation compared with numerical calculation by using actual hull-forms of 77 ships × 2 conditions.
This paper proposes a three dimensional model to explain microscopic behavior of cleavage crack propagation in steel. This model is based on a fracture mechanics model, which assumes a crack propagation along the cleavage plane with the highest tensile normal stress among three {100} planes in a grain. For calculating the normal stresses on the {100} planes, local stress intensity factors need to be calculated. The model considered three factors for estimating the local stress intensity factors, i.e., non-straight crack front, irregular crack surface and unfractured ligament between the grains and approximate calculations were carried out. The results are compared with observations of Charpy impact specimen fracture surfaces by conventional SEM as well as 3D SEM. The comparison showed good agreement between the calculations and the experiments. It was demonstrated by the present model that grain size and critical value of shear fracture had influence on cleavage crack propagation direction, discontinuous boundary and tear ridge formation.
Synopsis :The authors proposed a three dimensional model to explain microscopic behavior of cleavage crack propagation in steel, which was validated by experimental results, in the previous paper. Purpose of this paper is to explore further into microscopic cleavage crack propagation behavior in steels having anisotropy using the proposed model. Charpy impact testing and small size crack arrest testing were conducted for observing anisotropy of cleavage fracture toughness and it was confirmed that R direction has lower toughness than LT and TL directions. And simulation was also conducted using the data of crystal orientation, which was derived from Electron Back Scattering Diffraction analysis. The comparison between the experiment and the simulation showed good agreement and the lowest toughness in the R direction was explained by a concentration of {100} planes in that direction.
In order to ensure the structural safety of a ship, the most severe sea states she is expected to encounter throughout her service life need to be given consideration. This is the reason why the maximum loads corresponding to such sea states are typically specified in classification society structural rules such as the Common Structural Rules (CSR) of the International Association of Classification Societies (IACS). The maximum loads used for the structural design of a ship can have a significant impact on not only her structural safety, but also her hull construction cost; therefore, it is very important that the loads be accurately estimated. The linear term of the maximum loads typically specified in some classification society rules is equivalent to a long-term predicted value with an exceedance probability of 10−8. Since the maximum loads specified in classification society rules such as the CSR were developed specifically for specific ship types, their effective application to other ship types may be somewhat limited. Aim of our larger study is to develop a closed formula of long-term prediction for maximum loads. The formula has high accuracy and can be applied to any ship size and type. This paper focused on the heave acceleration and pitch angle, which are used for the calculation of internal loads and so on. A formula which takes into account such as the standard deviation of the hull response in irregular waves and the directional distribution of irregular waves was proposed. Main ship parameters such as ship length L, breadth B, draft d, block coefficient Cb, and water line area coefficient Cw were used for formulating the long-term prediction. The accuracy and effectiveness of the proposed formula were confirmed through various numerical calculations using a linear seakeeping analysis code developed by ClassNK. The calculation covers 154 ship models (77 existing ships × 2 loading conditions per ship).
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