Search for: All records

Lignin is an aromatic biopolymer found in ubiquitous sources of woody biomass. Designing and optimizing lignin valorization processes requires a fundamental understanding of lignin structures. Experimental characterization techniques, such as 2D-heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectra, could elucidate the global properties of the polymer molecules. Computer models could extend the resolution of experiments by representing structures at the molecular and atomistic scales. We introduce a graph-based multiscale modeling framework for lignin structure generation and visualization. The framework employs accelerated rejection-free polymerization and hierarchical Metropolis Monte Carlo optimization algorithms. We obtain structure libraries for various lignin feedstocks based on literature and new experimental NMR data for poplar wood, pinewood, and herbaceous lignin. The framework could guide researchers towards feasible lignin structures, efficient space exploration, and future kinetics modeling. Its software implementation in Python, LigninGraphs, is open-source and available on GitHub.

Graphical abstract

Sphingosine kinase 1 (SPHK1) and the sphingosine-1-phosphate (S1P) signaling pathway have been shown to play a role in pulmonary arterial hypertension (PAH). S1P is an important stimulus for pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling. We aimed to examine the specific roles of SPHK1 in PASMCs during pulmonary hypertension (PH) progression. We generated smooth muscle cell-specific, Sphk1-deficient (Sphk1f/f TaglnCre+) mice and isolated Sphk1-deficient PASMCs from SPHK1 knockout mice. We demonstrated that Sphk1f/f TaglnCre+ mice are protected from hypoxia or hypoxia/Sugen-mediated PH, and pulmonary vascular remodeling and that Sphk1-deficient PASMCs are less proliferative compared with ones isolated from wild-type (WT) siblings. S1P or hypoxia activated yes-associated protein 1 (YAP1) signaling by enhancing its translocation to the nucleus, which was dependent on SPHK1 enzymatic activity. Further, verteporfin, a pharmacologic YAP1 inhibitor, attenuated the S1P-mediated proliferation of hPASMCs, hypoxia-mediated PH, and pulmonary vascular remodeling in mice and hypoxia/Sugen-mediated severe PH in rats. Smooth muscle cell-specific SPHK1 plays an essential role in PH via YAP1 signaling, and YAP1 inhibition may have therapeutic potential in treating PH.

Worm-like robots have demonstrated great potential in navigating through environments requiring body shape deformation. Some examples include navigating within a network of pipes, crawling through rubble for search and rescue operations, and medical applications such as endoscopy and colonoscopy. In this work, we developed path planning optimization techniques and obstacle avoidance algorithms for the peristaltic method of locomotion of worm-like robots. Based on our previous path generation study using a modified rapidly exploring random tree (RRT), we have further introduced the Bézier curve to allow more path optimization flexibility. Using Bézier curves, the path planner can explore more areas and gain more flexibility to make the path smoother. We have calculated the obstacle avoidance limitations during turning tests for a six-segment robot with the developed path planning algorithm. Based on the results of our robot simulation, we determined a safe turning clearance distance with a six-body diameter between the robot and the obstacles. When the clearance is less than this value, additional methods such as backward locomotion may need to be applied for paths with high obstacle offset. Furthermore, for a worm-like robot, the paths of subsequent segments will be slightly different than the path of the head segment. Here,more »we show that as the number of segments increases, the differences between the head path and tail path increase, necessitating greater lateral clearance margins.« less

Fuzz testing, or fuzzing, has become one of the de facto standard techniques for bug finding in the software industry. In general, fuzzing provides various inputs to the target program with the goal of discovering unhandled exceptions and crashes. In business sectors where the time budget is limited, software vendors often launch many fuzzing instances in parallel as a common means of increasing code coverage. However, most of the popular fuzzing tools — in their parallel mode — naively run multiple instances concurrently, without elaborate distribution of workload. This can lead different instances to explore overlapped code regions, eventually reducing the benefits of concurrency. In this paper, we propose a general model to describe parallel fuzzing. This model distributes mutually-exclusive but similarly-weighted tasks to different instances, facilitating concurrency and also fairness across instances. Following this model, we develop a solution, called AFL-EDGE, to improve the parallel mode of AFL, considering a round of mutations to a unique seed as a task and adopting edge coverage to define the uniqueness of a seed. We have implemented AFL-EDGE on top of AFL and evaluated the implementation with AFL on 9 widely used benchmark programs. It shows that AFL-EDGE can benefit the edgemore »coverage of AFL. In a 24-hour test, the increase of edge coverage brought by AFL-EDGE to AFL ranges from 9.5% to 10.2%, depending on the number of instances. As a side benefit, we discovered 14 previously unknown bugs.« less