8q24.21 is a frequently amplified genomic region in colorectal cancer (CRC). This region is often referred to as a ‘gene desert’ due to lack of any important protein-coding genes, highlighting the ...potential role of noncoding RNAs, including long noncoding RNAs (lncRNAs) located around the proto-oncogeneMYC. In this study, we have firstly evaluated the clinical significance of altered expression of lncRNAs mapped to this genomic locus in CRC.
A total of 300 tissues, including 280 CRC and 20 adjacent normal mucosa specimens were evaluated for the expression of 12 lncRNAs using qRT-PCR assays. We analyzed the associations between lncRNA expression and various clinicopathological features, as well as with recurrence free survival (RFS) and overall survival (OS) in two independent cohorts.
The expression of CCAT1, CCAT1-L, CCAT2, PVT1, and CASC19 were elevated in cancer tissues (P=0.039, <0.001, 0.018, <0.001, 0.002, respectively). Among these, high expression of CCAT1 and CCAT2 was significantly associated with poor RFS (P=0.049 and 0.022, respectively) and OS (P=0.028 and 0.015, respectively). These results were validated in an independent patient cohort, in which combined expression of CCAT1 and CCAT2 expression was significantly associated with a poor RFS (HR:2.60, 95% confidence interval CI: 1.04–6.06,P=0.042) and a poor OS (HR:8.38, 95%CI: 2.68–37.0,P<0.001). We established a RFS prediction model which revealed that combined expression of CCAT1, CCAT2, and carcinoembryonic antigen was a significant determinant for efficiently predicting RFS in stage II (P=0.034) and stage III (P=0.001) CRC patients.
Several lncRNAs located in 8q24.21 locus are highly over-expressed in CRC. High expression of CCAT1 and CCAT2 significantly associates with poor RFS and OS. The expression of these two lncRNAs independently, or in combination, serves as important prognostic biomarkers in CRC.
A concentrated, vertical monolayer of identical spherical squirmers, which may be bottom heavy, and which are subjected to a linear shear flow, is modelled computationally by two different methods: ...Stokesian dynamics, and a lubrication-theory-based method. Inertia is negligible. The aim is to compute the effective shear viscosity and, where possible, the normal stress differences as functions of the areal fraction of spheres $\phi$, the squirming parameter $\beta$ (proportional to the ratio of a squirmer's active stresslet to its swimming speed), the ratio $Sq$ of swimming speed to a typical speed of the shear flow, the bottom-heaviness parameter $G_{bh}$, the angle $\alpha$ that the shear flow makes with the horizontal and two parameters that define the repulsive force that is required computationally to prevent the squirmers from overlapping when their distance apart is less than a critical value. The Stokesian dynamics method allows the rheological quantities to be computed for values of $\phi$ up to $0.75$; the lubrication-theory method can be used for $\phi > 0.5$. For non-bottom-heavy squirmers, which are unaffected by gravity, the effective shear viscosity is found to increase more rapidly with $\phi$ than for inert spheres, whether the squirmers are pullers ($\beta > 0$) or pushers ($\beta < 0$); it also varies with $\beta$, although not by very much. However, for bottom-heavy squirmers the behaviour for pullers and pushers as $G_{bh}$ and $\alpha$ are varied is very different, since the viscosity can fall even below that of the suspending fluid for pushers at high $G_{bh}$. The normal stress differences, which are small for inert spheres, can become very large for bottom-heavy squirmers, increasing with $\beta$, and varying dramatically as the orientation $\alpha$ of the flow is varied from 0 to ${\rm \pi} /2$. A major finding is that, despite very different assumptions, the two methods of computation give overlapping results for viscosity as a function of $\phi$ in the range $0.5 < \phi < 0.75$. This suggests that lubrication theory, based on near-field interactions alone, contains most of the relevant physics, and that taking account of interactions with more distant particles than the nearest is not essential to describe the dominant physics.
Coherent conversion of microwave and optical photons in the single quantum level can significantly expand our ability to process signals in various fields. Efficient up-conversion of a feeble signal ...in the microwave domain to the optical domain will lead to quantum-noise-limited microwave amplifiers. Coherent exchange between optical photons and microwave photons will also be a stepping stone to realize long-distance quantum communication. Here we demonstrate bidirectional and coherent conversion between microwave and light using collective spin excitations in a ferromagnet. The converter consists of two harmonic oscillator modes, a microwave cavity mode and a magnetostatic mode called the Kittel mode, where microwave photons and magnons in the respective modes are strongly coupled and hybridized. An itinerant microwave field and a traveling optical field can be coupled through the hybrid system, where the microwave field is coupled to the hybrid system through the cavity mode, while the optical field addresses the hybrid system through the Kittel mode via Faraday and inverse Faraday effects. The conversion efficiency is theoretically analyzed and experimentally evaluated. The possible schemes for improving the efficiency are also discussed.
Inflammation has an important role in cancer development through various mechanisms. It has been shown that dysregulation of microRNAs (miRNAs) that function as oncogenes or tumor suppressors ...contributes to tumorigenesis. However, the relationship between inflammation and cancer-related miRNA expression in tumorigenesis has not yet been fully understood. Using K19-C2mE and Gan mouse models that develop gastritis and gastritis-associated tumors, respectively, we found that 21 miRNAs were upregulated, and that 29 miRNAs were downregulated in gastric tumors in an inflammation-dependent manner. Among these miRNAs, the expression of miR-7, a possible tumor suppressor, significantly decreased in both gastritis and gastric tumors. Moreover, the expression of miR-7 in human gastric cancer was inversely correlated with the levels of interleukin-1β and tumor necrosis factor-α, suggesting that miR-7 downregulation is related to the severity of inflammatory responses. In the normal mouse stomach, miR-7 expression was at a basal level in undifferentiated gastric epithelial cells, and was induced during differentiation. Moreover, transfection of a miR-7 precursor into gastric cancer cells suppressed cell proliferation and soft agar colony formation. These results suggest that suppression of miR-7 expression is important for maintaining the undifferentiated status of gastric epithelial cells, and thus contributes to gastric tumorigenesis. Although epigenetic changes were not found in the CpG islands around miR-7-1 of gastritis and gastric tumor cells, we found that activated macrophage-derived small molecule(s) (<3 kDa) are responsible for miR-7 repression in gastric cancer cells. Furthermore, the miR-7 expression level significantly decreased in the inflamed gastric mucosa of Helicobacter-infected mice, whereas it increased in the stomach of germfree K19-C2mE and Gan mice wherein inflammatory responses were suppressed. Taken together, these results indicate that downregulation of tumor suppressor miR-7 is a novel mechanism by which the inflammatory response promotes gastric tumorigenesis.
The fractional resistance on a fault during slip controls earthquake dynamics. Friction dissipates heat during an earthquake; therefore, the fault temperature after an earthquake provides insight ...into the level of friction. The Japan Trench Fast Drilling Project (Integrated Ocean Drilling Program Expedition 343 and 343T) installed a borehole temperature observatory 16 months after the March 2011 moment magnitude 9.0 Tohoku-Oki earthquake across the fault where slip was ~50 meters near the trench. After 9 months of operation, the complete sensor string was recovered. A 0.31 °C temperature anomaly at the plate boundary fault corresponds to 27 megajoules per square meter of dissipated energy during the earthquake. The resulting apparent friction coefficient of 0.08 is considerably smaller than static values for most rocks.
A beamline for the x-ray free electron laser (XFEL) of SPring-8 Angstrom Compact free electron LAser (SACLA) provides hard x-ray pulses in the range 4.5-19.5 keV. Its optical system in an optics ...hutch delivers a pink beam below 15 keV with either of two double-mirror systems or a monochromatic beam with a double-crystal monochromator. These XFEL beams are used for various types of measurement at experimental stations, e.g. x-ray diffraction, coherent diffraction imaging, x-ray spectroscopy and pump-and-probe measurement. The experimental stations consist of experimental hutches and control stations, and a femtosecond optical laser which is synchronized with XFEL pulses. Photon diagnostics have been performed for measuring radiation parameters in a shot-by-shot manner.
A superconducting qubit in the strong dispersive regime of circuit quantum electrodynamics is a powerful probe for microwave photons in a cavity mode. In this regime, a qubit excitation spectrum is ...split into multiple peaks, with each peak corresponding to an individual photon number in the cavity (discrete ac Stark shift). Here, we measure the qubit spectrum in a cavity that is driven continuously with a squeezed vacuum generated by a Josephson parametric amplifier. By fitting the obtained spectrum with a model which takes into account the finite qubit excitation power, we determine the photon number distribution, which reveals an even-odd photon number oscillation and quantitatively fulfills Klyshko's criterion for nonclassicality.
Rheotaxis and migration of cells in a flow field have been investigated intensively owing to their importance in biology, physiology and engineering. In this study, first, we report our experiments ...showing that the microalgae Chlamydomonas can orient against the channel flow and migrate to the channel centre. Second, by performing boundary element simulations, we demonstrate that the mechanism of the observed rheotaxis and migration has a physical origin. Last, using a simple analytical model, we reveal the novel physical mechanisms of rheotaxis and migration, specifically the interplay between cyclic body deformation and cyclic swimming velocity in the channel flow. The discovered mechanism can be as important as phototaxis and gravitaxis, and likely plays a role in the movement of other natural microswimmers and artificial microrobots with non-reciprocal body deformation.
Abstract Red blood cells migrate to the center of the blood vessel in a process called axial migration, while other blood cells, such as white blood cells and platelets, are disproportionately found ...near the blood vessel wall. However, much is still unknown concerning the lateral migration of cells in the blood; the specific effect of hydrodynamic factors such as a wall or a shear gradient is still unclear. In this study, we investigate the lateral migration of a capsule using the boundary integral method, in order to compute exactly an infinite computational domain for an unbounded parabolic flow and a semi-infinite computational domain for a near-wall parabolic flow in the limit of Stokes flow. We show that the capsule lift velocity in an unbounded parabolic flow is linear with respect to the shear gradient, while the lift velocity in a near-wall parabolic flow is dependent on the distance to the wall. Then, using these relations, we give an estimation of the relative effect of the shear gradient as a function of channel width and distance between the capsule and the wall. This estimation can be used to determine cases in which the effect of the shear gradient or wall can be neglected; for example, the formation of the cell-free layer in blood vessels is determined to be unaffected by the magnitude of the shear gradient.
We present a numerical analysis of the rheology of a dense suspension of spherical capsules in simple shear flow in the Stokes flow regime. The behaviour of neo-Hookean capsules is simulated for a ...volume fraction up to
${\it\phi}=0.4$
by graphics processing unit computing based on the boundary element method with a multipole expansion. To describe the specific viscosity using a polynomial equation of the volume fraction, the coefficients of the equation are calculated by least-squares fitting. The results suggest that the effect of higher-order terms is much smaller for capsule suspensions than rigid sphere suspensions; for example,
$O({\it\phi}^{3})$
terms account for only 8 % of the specific viscosity even at
${\it\phi}=0.4$
for capillary numbers
$Ca\geqslant 0.1$
. We also investigate the relationship between the deformation and orientation of the capsules and the suspension rheology. When the volume fraction increases, the deformation of the capsules increases while the orientation angle of the capsules with respect to the flow direction decreases. Therefore, both the specific viscosity and the normal stress difference increase with volume fraction due to the increased deformation, whereas the decreased orientation angle suppresses the specific viscosity, but amplifies the normal stress difference.
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