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Many slow slip events (SSEs) occur beneath the ocean, and continuous ocean‐bottom pressure gauge (OBP) observations provide useful data. OBPs record both oceanic variations and crustal movements, so we developed a multi‐channel singular spectrum analysis method to remove oceanic variations and applied our method to OBPs and oceanic model data. Then components of the oceanic model with good correlations to the OBP data were subtracted from the observed data. This method compensates for the incompleteness of the oceanic model and removes oceanic variations better than use of the original model. We applied the method to OBP data for the 2018 Boso, Japan, SSE to estimate its slip distribution. Comparing slip distributions obtained with and without the OBP data, we found that the distribution obtained using OBP data extended further offshore, and the offshore estimation error was smaller. Our study shows that offshore observations using OBPs are important for characterizing SSEs. Plain Language Summary: Slow slip events (SSEs) occur when faults slip slowly without generating seismic waves. Because most SSEs occur under the ocean, continuous observations by ocean‐bottom pressure instruments (OBPs) provide useful data. OBPs record both oceanic changes and seafloor movements. To remove the oceanic changes and more clearly observe seafloor movements, we developed a signal processing method to extract similar components from multiple time series. We applied our method to OBP data and oceanic model data, then subtracted the components of the oceanic model that match the OBP data from the observed data. This method removed the oceanic changes from the OBP data better than use of the original oceanic model alone. We applied this method to OBP data for the 2018 Boso, Japan, SSE and used vertical motions in the OBP data to estimate the slip distribution. The distribution obtained with the OBP data extended further offshore and was more accurate than that obtained without the OBP data. This study shows that observations of the ocean bottom obtained with OBPs are important for characterizing SSEs. Key Points: We removed oceanic variations from ocean‐bottom pressure data using a reconstructed oceanic model, achieving ±4 mm observed accuracyThe reconstructed oceanic model includes only components with good correlations between observed data and the oceanic modelUse of the ocean‐bottom pressure data and the proposed method improved the accuracy of the slow slip distribution in offshore areas [ABSTRACT FROM AUTHOR]

Although phage display selection using a library of M13 bacteriophage has become a powerful tool for finding peptides that bind to target materials on demand, a remaining concern of this method is the interference by the M13 main body, which is a huge filament >103 times larger than the displayed peptide, and therefore would nonspecifically adhere to the target or sterically inhibit the binding of the displayed peptide. Meanwhile, filamentous phages are known to be orientable by an external magnetic field. If M13 filaments are magnetically oriented during the library selection, their angular arrangement relative to the target surface would be changed, being expected to control the interference by the M13 main body. This study reports that the magnetic orientation of M13 filaments vertical to the target surface significantly affects the selection. When the target surface was affinitive to the M13 main body, this orientation notably suppressed the nonspecific adhesion. Furthermore, when the target surface was less affinitive to the M13 main body and intrinsically free from the nonspecific adhesion, this orientation drastically changed the population of M13 clones obtained through library selection. The method of using no chemicals but only a physical stimulus is simple, clean, and expected to expand the scope of phage display selection. [ABSTRACT FROM AUTHOR]

The levitation methodology, which enables us to operate a contactless reaction without a container, is likely to be a revolutionary technology in the fields of chemistry and biology to reduce the plastic waste in life science laboratories. Here, the authors show that plasmid DNA can be effectively transfected into animal cells in a floating droplet of culture medium levitated using ultrasonic standing waves. The data indicate that there is no significant damage to the plasmid and cells during the levitating transfection time, and the transgene expression efficiency and cellular uptake in the droplet are significantly higher than those in the conventional tube, with and without shaking. These results suggest the consolidation of the endocytic uptake pathway into macropinocytosis, indicating that ultrasonic levitation induced a change in cell characteristics. This study suggests that transfection methodology using ultrasonic levitation has the potential to advance the current experimental procedures in the field of cell engineering, in addition to presenting a revolutionary containerless reactor for sustainable technology. [ABSTRACT FROM AUTHOR]

Theoretical analyses using a rate‐ and state‐dependent friction law have shown quasistatic and stable slip behaviors following velocity weakening. We estimated spatiotemporal slip distributions for six slow slip events (SSEs) off the Boso Peninsula, Japan, from Global Navigation Satellite System data and plotted their shear stress variations vs. slip velocity, here called "trajectories." Most trajectories are similar to theoretical stable trajectories, implying that the Boso SSEs represent a quasistatic and stable process, and that the gradient of the trajectories during slip acceleration is equal to the product of the friction coefficients of the slipping plates (a–b) and the effective normal stress (σn′). Taking (a–b) = −0.003, we estimate that the effective normal stresses during the SSEs were 10–50 MPa at 12.5–20.5 km depth. These values are much smaller than the lithostatic pressures at those depths, implying high pore pressures on the slow slip interface. Plain Language Summary: From theoretical studies, it is known that quasistatic and stable slip behaviors can occur when frictional stress decreases with increasing slip velocity. We estimated slip distributions in time and space for six slow slip events (SSEs; characterized by slow slip on the plate interface without the production of seismic waves) off the Boso Peninsula, Japan, from Global Navigation Satellite System data, and plotted slip velocities vs. shear stress changes on the plate interface. Most graphs are similar to those in the theoretical studies, implying that SSEs have quasistatic and stable behavior, and that the slopes of the graphs can be used to determine effective normal stress (the difference between normal stress and water pressure on the plate interface) given that reasonable friction coefficients are known. Taking average friction coefficients from previous studies, we estimate that the effective normal stresses during the SSEs were 10–50 MPa at 12.5–20.5 km depth. These values are much smaller than the pressure due to the weight of the overlying rock, implying that water pressure is very high on the slow slip interface. Key Points: We estimated spatiotemporal slip distributions and shear stress variations for six slow slip events from Global Navigation Satellite System dataBased on gradients in the slip velocity versus stress plot, effective normal stresses were 10–50 MPa at 12.5–20.5 km depthThese values are much smaller than lithostatic pressures at those depths and imply high pore pressures on the slow slip interface [ABSTRACT FROM AUTHOR]

Background Lyophilization is an effective method for preserving nonviral gene vectors. To improve the stability and transgene expression of lyophilized plasmid DNA (pDNA) complexes, we coated the surfaces of pDNA/chitosan complexes with hyaluronic acid (HA) of varying molecular masses. The transgene expression of pDNA/chitosan/HA ternary complexes was characterized in vitro and in vivo. Methods pDNA complexes were lyophilized overnight and the resultant products with spongy, porous consistencies were stored at −30, 4 or 25°C for 2 weeks. Rehydrated complexes were characterized using gel retardation assays, aiming to confirm complex formation, measure particle size and evaluate zeta potential, as well as conduct luciferase gene reporter assays. The anti-tumor effects of pDNA ternary complexes were evaluated using suicide gene (pTK) coding thymidine kinase in Huh7-implanted mice. Results Transfection efficiencies of pDNA/chitosan/HA ternary complexes were dependent on the average molecular masses of HA. The coating of pDNA/chitosan complexes with HA maintained the cellular transfection efficiencies of lyophilized pDNA ternary complexes. Furthermore, intratumoral injection of lyophilized, rehydrated pDNA ternary complexes into tumor-bearing mice showed a significant suppression of tumor growth. Conclusions The coating of pDNA/chitosan complexes with high-molecular-weight HA augmented the stability and cellular transfection ability of the complexes after lyophilization-rehydration. [ABSTRACT FROM AUTHOR]

Background Chitosan has been investigated as a promising nonviral vector. However, several problems still remain, such as a relatively low transfection efficiency and instability under physiological conditions. We previously demonstrated that a chondroitin sulfate (CS) coating enhanced the transfection efficiency and physicochemical stability of plasmid DNA (pDNA)/chitosan complexes in vitro. In the present study, the effects of coating pDNA/chitosan complexes with CS on the stability in freeze-dry rehydration processes and gene expression in vivo were investigated. Methods Freeze-drying storage at -20 °C, 4 °C, or room temperature, freezing storage at -20 °C, or liquid storage at 4 °C or room temperature, were examined for preservation conditions of pDNA/chitosan/CS ternary complexes by a gel retardation assay, measurements of sizes and zeta potentials, and a luciferase assay. Moreover, to determine the transfection efficiency of the ternary complexes in vivo, suicide gene therapy was carried out in Huh-7-implanted mice using herpes simplex virus thymidine kinase coding pDNA and ganciclovir. Results The freeze-dried pDNA/chitosan/CS ternary complexes showed sufficient cell transfection ability in vitro and in vivo. In addition, ternary complexes were associated with a significant suppression of tumor growth and a histopathologically high anti-tumor effect by intratumoral injection to tumor-bearing mice. Conclusions The CS coating enhanced the preservation stability of the pDNA/chitosan complexes after freeze-drying-rehydration and their transgene expression in vivo. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2012) 121, 619-628. Abstract Type 2 diabetes mellitus is thought to be a significant risk factor for Alzheimer's disease. Insulin resistance also affects the central nervous system by regulating key processes, such as neuronal survival and longevity, learning and memory. However, the mechanisms underlying these effects remain uncertain. To investigate whether insulin resistance is associated with the assembly of amyloid β-protein (Aβ) at the cell surface of neurons, we inhibited insulin-signalling pathways of primary neurons. The treatments of insulin receptor (IR)-knockdown and a phosphatidylinositol 3-kinase inhibitor (LY294002), but not an extracellular signal-regulated kinase inhibitor, induced an increase in GM1 ganglioside (GM1) levels in detergent-resistant membrane microdomains of the neurons. The aged db/db mouse brain exhibited reduction in IR expression and phosphorylation of Akt, which later induced an increase in the high-density GM1-clusters on synaptosomes. Neurons treated with IR knockdown or LY294002, and synaptosomes of the aged db/db mouse brains markedly accelerated an assembly of Aβs. These results suggest that ageing and peripheral insulin resistance induce brain insulin resistance, which accelerates the assembly of Aβs by increasing and clustering of GM1 in detergent-resistant membrane microdomains of neuronal membranes. [ABSTRACT FROM AUTHOR]

Ly-GDI, Rho GTPase dissociation inhibitor beta, was found to be expressed parallel to the GM3 level in mouse B16 cells whose GM3 contents were modified by B4galt6 sense, B4galt6 antisense cDNA, or St3galt5 siRNA transfection. Ly-GDI expression was increased on GM3 addition to these cells and decreased with D-PDMP treatment, a glucosylceramide synthesis inhibitor. Suppression of GM3 or Ly-GDI by RNAi was concomitantly associated with an increase in anchorage-independent growth in soft agar. These results clearly indicate that GM3 suppresses anchorage-independent growth through Ly-GDI. GM3 signals regulating Ly-GDI expression was inhibited by LY294002, siRNA against Akt1 and Akt2 and rapamycin, showing that GM3 signals are transduced via the PI3K/Akt/mTOR pathway. Either siRNA towards Rictor or Raptor suppressed Ly-GDI expression. The Raptor siRNA suppressed the effects of GM3 on Ly-GDI expression and Akt phosphorylation at Thr308, suggesting GM3 signals to be transduced to mTOR-Raptor and Akt-Thr308, leading to Ly-GDI stimulation. siRNA targeting Pdpk1 reduced Akt phosphorylation at Thr308 and rendered the cells insensitive to GM3 stimulation, indicating that Akt-Thr308 plays a critical role in the pathway. The components aligned in this pathway showed similar effects on anchorage-independent growth as GM3 and Ly-GDI. Taken together, GM3 signals are transduced in B16 cells through PI3K, Pdpk1, AktThr308 and the mTOR/Raptor pathway, leading to enhanced expression of Ly-GDI mRNA, which in turn suppresses anchorage-independent growth in melanoma B16 cells. ( Cancer Sci 2011; 102: 1476-1485) [ABSTRACT FROM AUTHOR]

The Hahajima Seamount, located at the junction between the Izu–Bonin and Mariana forearc slopes, is a notable rectangular shape and consists of various kinds of rocks. An elaborated bathymetric swath mapping with geophysical measurements and dredge hauls showed the Hahajima Seamount is cut by two predominating lineaments, northeast–southwest and northwest–southeast. These lineaments are of faults based on the topographic cross-sections and a 3-D view (whale's eye view). The former lineament is parallel to the transform faults of the Parece Vela Basin, whereas the latter is parallel to the nearby transform fault on the subducting Pacific Plate. The rocks constituting the seamount are ultramafic rocks (mostly harzburgite), boninite, basalt, andesite, gabbro, breccia and sedimentary rocks, which characterize an island arc and an ocean basin. Gravity measurement and seismic reflection survey offer neither a definite gravity anomaly at the seamount nor definite internal structures beneath the seamount. A northwest–southeast-trending fault and small-scale serpentine flows were observed during submersible dives at the Hahajima Seamount. The rectangular shape, size of the seamount, various kinds of rocks and geophysical measurements strongly suggest that the Hahajima Seamount is not a simple serpentine seamount controlled by various tectonic movements, as previously believed, but a tectonic block. [ABSTRACT FROM AUTHOR]

Operand bypass logic is likely to be one of the critical structures for future microprocessors to achieve high clock speed. The logic delay causes the execution time budget to be reduced significantly, so that the execution stage is divided into several stages. The variable latency pipeline (VLP) structure has the advantages of pipelining and pseudo-asynchronous design. According to the source operands delivered to arithmetic units, VLP changes execution latency and thus achieves both high speed and low latency for most operands. In this paper we evaluate VLP with dynamically scheduled superscalar processors, using a cycle-by-cycle simulator. Our experimental results show that VLP successfully reduces the effective execution time, and thus relaxes the constraints on the operand bypass logic. We also evaluate the instruction reuse technique in order to support VLP. © 2003 Wiley Periodicals, Inc. Syst Comp Jpn, 34(12): 11–21, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10498 [ABSTRACT FROM AUTHOR]