Pengfei Dong

Bio: Pengfei Dong is an academic researcher from Florida Institute of Technology. The author has contributed to research in topics: Medicine & Stent. The author has an hindex of 6, co-authored 28 publications receiving 545 citations. Previous affiliations of Pengfei Dong include University of Nebraska–Lincoln & Taiyuan University of Technology.

Mechanical Characterizations of 3D-printed PLLA/Steel Particle Composites.

Abstract: The objective of this study is to characterize the micromechanical properties of poly-l-lactic acid (PLLA) composites reinforced by grade 420 stainless steel (SS) particles with a specific focus on the interphase properties. The specimens were manufactured using 3D printing techniques due to its many benefits, including high accuracy, cost effectiveness and customized geometry. The adopted fused filament fabrication resulted in a thin interphase layer with an average thickness of 3 µm. The mechanical properties of each phase, as well as the interphase, were characterized by nanoindentation tests. The effect of matrix degradation, i.e., imperfect bonding, on the elastic modulus of the composite was further examined by a representative volume element (RVE) model. The results showed that the interphase layer provided a smooth transition of elastic modulus from steel particles to the polymeric matrix. A 10% volume fraction of steel particles could enhance the elastic modulus of PLLA polymer by 31%. In addition, steel particles took 37% to 59% of the applied load with respect to the particle volume fraction. We found that degradation of the interphase reduced the elastic modulus of the composite by 70% and 7% under tensile and compressive loads, respectively. The shear modulus of the composite with 10% particles decreased by 36%, i.e., lower than pure PLLA, when debonding occurred.

Micromechanical analysis of bioresorbable PLLA/Mg composites coated with MgO: Effects of particle weight fraction, particle/matrix interface bonding strength and interphase

Abstract: Magnesium (Mg) particle has been recently introduced in a poly- l -lactic acid (PLLA) matrix to enhance to its mechanical properties. The coating of Mg particle could also regulate its degradation rate. In this work, the mechanical behavior of PLLA/Mg composite was characterized using a three-dimensional representative volume element (RVE) model. The influences of Mg weight fraction, imperfect bonding between particle and polymer matrix, and the interphase layer on the mechanical behaviors of the composites were quantified. Results clearly demonstrated that the effective Young's modulus and yield strength of the composite were enhanced by the Mg particles, as well as its MgO coating. In addition, the imperfect interfacial bonding between the Mg particle and PLLA weakened the mechanical advantage of the composite, which was in good agreement with the documented experimental observations. This work might shed some light on the optimal design and manufacturing of the bioresorbable composites.

Chromatin domain alterations linked to 3D genome organization in a large cohort of schizophrenia and bipolar disorder brains

Abstract: Chromosomal organization, scaling from the 147-base pair (bp) nucleosome to megabase-ranging domains encompassing multiple transcriptional units, including heritability loci for psychiatric traits, remains largely unexplored in the human brain. In this study, we constructed promoter- and enhancer-enriched nucleosomal histone modification landscapes for adult prefrontal cortex from H3-lysine 27 acetylation and H3-lysine 4 trimethylation profiles, generated from 388 controls and 351 individuals diagnosed with schizophrenia (SCZ) or bipolar disorder (BD) (n = 739). We mapped thousands of cis-regulatory domains (CRDs), revealing fine-grained, 104-106-bp chromosomal organization, firmly integrated into Hi-C topologically associating domain stratification by open/repressive chromosomal environments and nuclear topography. Large clusters of hyper-acetylated CRDs were enriched for SCZ heritability, with prominent representation of regulatory sequences governing fetal development and glutamatergic neuron signaling. Therefore, SCZ and BD brains show coordinated dysregulation of risk-associated regulatory sequences assembled into kilobase- to megabase-scaling chromosomal domains.

Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes

Abstract: Significance When the human genome folds up inside the cell nucleus, it is spatially partitioned into numerous loops and contact domains. How these structures form is unknown. Here, we show that data from high-resolution spatial proximity maps are consistent with a model in which a complex, including the proteins CCCTC-binding factor (CTCF) and cohesin, mediates the formation of loops by a process of extrusion. Contact domains form as a byproduct of this process. The model accurately predicts how the genome will fold, using only information about the locations at which CTCF is bound. We demonstrate the ability to reengineer loops and domains in a predictable manner by creating highly targeted mutations, some as small as a single base pair, at CTCF sites. We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic “tension globule.” In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.

Stent Thrombogenicity Early in High Risk Interventional Settings is Driven by Stent Design and Deployment, and Protected by Polymer-Drug Coatings

Abstract: Background—Stent thrombosis is a lethal complication of endovascular intervention. Concern has been raised about the inherent risk associated with specific stent designs and drug-eluting coatings, yet clinical and animal support is equivocal. Methods and Results—We examined whether drug-eluting coatings are inherently thrombogenic and if the response to these materials was determined to a greater degree by stent design and deployment with custom-built stents. Drug/polymer coatings uniformly reduce rather than increase thrombogenicity relative to matched bare metal counterparts (0.65-fold; P=0.011). Thick-strutted (162 μm) stents were 1.5-fold more thrombogenic than otherwise identical thin-strutted (81 μm) devices in ex vivo flow loops (P<0.001), commensurate with 1.6-fold greater thrombus coverage 3 days after implantation in porcine coronary arteries (P=0.004). When bare metal stents were deployed in malapposed or overlapping configurations, thrombogenicity increased compared with apposed, length-matche...

Mechanical Characterizations of 3D-printed PLLA/Steel Particle Composites.

Abstract: The objective of this study is to characterize the micromechanical properties of poly-l-lactic acid (PLLA) composites reinforced by grade 420 stainless steel (SS) particles with a specific focus on the interphase properties. The specimens were manufactured using 3D printing techniques due to its many benefits, including high accuracy, cost effectiveness and customized geometry. The adopted fused filament fabrication resulted in a thin interphase layer with an average thickness of 3 µm. The mechanical properties of each phase, as well as the interphase, were characterized by nanoindentation tests. The effect of matrix degradation, i.e., imperfect bonding, on the elastic modulus of the composite was further examined by a representative volume element (RVE) model. The results showed that the interphase layer provided a smooth transition of elastic modulus from steel particles to the polymeric matrix. A 10% volume fraction of steel particles could enhance the elastic modulus of PLLA polymer by 31%. In addition, steel particles took 37% to 59% of the applied load with respect to the particle volume fraction. We found that degradation of the interphase reduced the elastic modulus of the composite by 70% and 7% under tensile and compressive loads, respectively. The shear modulus of the composite with 10% particles decreased by 36%, i.e., lower than pure PLLA, when debonding occurred.

ChromHMM: automating chromatin-state discovery and characterization

Abstract: Chromatin state annotation using combinations of chromatin modification patterns has emerged as a powerful approach for discovering regulatory regions and their cell type specific activity patterns, and for interpreting disease-association studies1-5. However, the computational challenge of learning chromatin state models from large numbers of chromatin modification datasets in multiple cell types still requires extensive bioinformatics expertise making it inaccessible to the wider scientific community. To address this challenge, we have developed ChromHMM, an automated computational system for learning chromatin states, characterizing their biological functions and correlations with large-scale functional datasets, and visualizing the resulting genome-wide maps of chromatin state annotations.