MICROMECHANICS OF DNA UNDER SHARP BENDING

Ph.DDOCTOR OF PHILOSOPH

Revisiting the anomalous bending elasticity of sharply bent DNA

Several recent experiments suggest that sharply bent DNA has a surprisingly high bending flexibility, but the cause of this flexibility is poorly understood. Although excitation of flexible defects can explain these results, whether such excitation can occur with the level of DNA bending in these experiments remains unclear. Intriguingly, the DNA contained preexisting nicks in most of these experiments but whether nicks might play a role in flexibility has never been considered in the interpretation of experimental results. Here, using full-atom molecular dynamics simulations, we show that nicks promote DNA basepair disruption at the nicked sites, which drastically reduces DNA bending energy. In addition, lower temperatures suppress the nick-dependent basepair disruption. In the absence of nicks, basepair disruption can also occur but requires a higher level of DNA bending. Therefore, basepair disruption inside B-form DNA can be suppressed if the DNA contains preexisting nicks. Overall, our results suggest that the reported mechanical anomaly of sharply bent DNA is likely dependent on preexisting nicks, therefore the intrinsic mechanisms of sharply bent nick-free DNA remain an open question.Comment: 39 pages, 11 figures, 1 supporting materia

Speculation on optimal numbers of examined lymph node for early-stage epithelial ovarian cancer from the perspective of stage migration

IntroductionIn early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC).MethodsFrom the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method.ResultsMore ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range.DiscussionNeither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy

Local Enhancements of the Mean Drift Wave Force on a Vertical Column Shielded by an Exterior Thin Porous Shell

The wave interaction with a vertical column shielded by an exterior porous shell is studied within the framework of potential flow theory. The structures are fixed rigidly at the sea bottom. The interior cylinder is impermeable, and the exterior shell is slightly porous and thin. Additionally, the exterior shell is assumed to have fine pores, and a linear pressure drop is adopted at the porous geometry. The mean drift wave force on the system is thereby formulated by two alternative ways, based respectively on the direct pressure integration, i.e., the near-field formulation, and the application of the momentum conservation theorem in the fluid domain, i.e., the far-field formulation. The consistency of the two formulations in calculating the mean drift wave force is assessed for the present problem. Numerical results illustrate that the existence of the porous shell can substantially reduce the mean drift wave force on the interior column. It also appears that the far-field formulation consists of a conventional part as well as an additional part caused by the energy dissipation through the porous geometry. The mean drift wave force on the system is dominated by the first part, which resembles that on an impermeable body. Local enhancements of the mean drift wave force are found at some specific wave frequencies at which certain propagation modes of the fluid satisfy a no-flow condition at the porous shell

Optimization of baffled rectangular and prismatic storage tank against the sloshing phenomenon

The fluid motion in partially filled tanks with internal baffles has wide engineering applications. The installation of baffles is expected to reduce the effect of sloshing as well as the consequent environmental damages. In the present study, a series of experimental tests are performed to investigate the sloshing phenomenon in a baffled rectangular storage tank. In addition, the sloshing phenomenon is also modeled by using OpenFoam. Based on the experimental and numerical studies, optimization of the geometric parameters of the tank is performed based on some criteria such as tank area, entropy generation, and the horizontal force exerted on the tank area due to the sloshing phenomenon. The optimization is also carried out based on the entropy generation minimization analysis. It is noted that the optimum baffle height is in the range of hb/hw=0.5–0.75 in the present study (where hb and hw are the baffle height and water depth, respectively). Based on the results, the optimal design of the tank is achieved with RA= 0.9–1.0 (where RA=L/W, L and W are the length and width of the tank, respectively). The results also show that the increase of hb can lead to a decrease of the maximum pressure and horizontal force exerted on the tank. It is also noted that the horizontal force exerted on the tank firstly continues to increase as the sway motion amplitude increases. However, as the normalized motion amplitude parameter, a/L (The parameter a is the motion amplitude), exceeds 0.067, the effect of motion amplitude on the force is not obvious. The same optimization is also performed in the multiple-variable-baffled tank and prismatic storage tank