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.

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

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...

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

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.

/pdf/mechanical-characterizations-of-3d-printed-plla-steel-dslshaz63i.pdf

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

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.

ChromHMM: automating chromatin-state discovery and characterization

https://pureadmin.qub.ac.uk/ws/files/202071352/20200310_Paper_on_Physics_in_DFC_revised_1_.pdf

Extrusion-based additive manufacturing with cement-based materials – Production steps, processes, and their underlying physics: A review

Freeform reversible embedding of suspended hydrogels (FRESH) is a layer-by-layer extrusion-based technique to enable three-dimensional (3D) printing of soft tissue constructs by using a thermo-reve...

Optimization of Freeze-FRESH Methodology for 3D Printing of Microporous Collagen Constructs

Background: In stent restenosis (ISR) is one of the major complications after stent implantation. Thus, there is a growing interest in identifying a biomarker for the onset of ISR. High levels of serum homocysteine (Hcy) have been associated with the progression of cardiovascular disease. Therefore, the study was carried out to quantify the correlation between serum Hcy and ISR severity. Compared with coronary angiography (CAG), Hcy levels provided a significantly better clinical detection of ISR severity after PCI. Methods: A total of 155 patients were recruited from Shanxi Bethune hospital, from 6 months to 2 years post PCI. Serum Hcy levels and postoperative angiography results were used to differentiate the patients into two experimental groups: ISR (>50% diametrical stenosis), and non-ISR. The non-ISR included two subgroups: intimal hyperplasia (10–50% diametrical stenosis), and recovery (<10% diametrical stenosis). In addition, a group of 80 healthy individuals was used as a negative control. The correlation between homocysteine level and ISR severity t was analyzed for all groups. In addition, the correlation between serum Hcy level and the severity of ISR in the experimental group was analyzed by the Pearson correlation test. Results: The serum Hcy level in the experimental group and control group was determined to be (20.21 ± 11.42) μmol/L and (15.11 ± 10.25) μmol/L respectively. The level of serum Hcy in the experimental group was significantly higher than in the control group (t-value of 2.385; p-value of 0.019). The serum Hcy level in the restenosis and the intimal hyperplasia group was (25.72 ± 13.71) μmol/L and (17.35 ± 7.70) μmol/L respectively. The serum Hcy level in the restenosis group was significantly higher than in the intimal hyperplasia group (t-value of 2.215; p-value of 0.033). The level of serum Hcy in the group without a plaque in the stent was (16.30 ± 6.08) μmol/L, whereas in the control group was (15.11 ± 10.25) μmol/L. The no plaque group had a slightly higher serum Hcy level than the control group (t-value of 0.634; p-value of 0.528). All included patients were divided into four quartiles based on the serum Hcy concentration: quartile 1 (8.90–13.20 μmol/L), quartile 2 (13.30–16.45 μmol/L), quartile 3 (16.60–24.25 μmol/L) and quartile 4 (24.30-65.30 μ mol/L). The incidence of ISR was 5, 6.25, 7.5 and 15%, in the 1,2,3 and four quartiles respectively. The serum Hcy level in the experimental group was (20.21 ± 11.42) μmol/L, the severity of in-stent restenosis was (0.25 ± 0.31), (R-value was 0.234; p-value was 0.037), indicating a correlation between serum Hcy and the severity of restenosis (p < 0.05). Taking coronary angiography as the gold standard, a ROC curve analysis was performed on the serum Hcy levels for the experimental group. The area under the curve (AUC) was 0.718 (95% CI 0.585-0.854, p < 0.001), indicating that the serum Hcy concentration could predict ISR. On the ROC curve, the best critical value of serum Hcy concentration for predicting ISR was 20.05 μmol/L, with a sensitivity of 45% and specificity of 88.1%. Conclusion: A positive correlation was observed between homocysteine and the severity of restenosis after PCI, The level of Hcy could serve as a predictive biomarker for the severity of ISR.

Serum Homocysteine Level Predictive Capability for Severity of Restenosis Post Percutaneous Coronary Intervention

Trauma to the eye resulting from a soccer ball is a common sports-related injury. Although the types of ocular pathologic features that result from impact have been documented, the underlying pathophysiologic mechanics are not as well studied. The purpose of this study was to evaluate the biomechanical events after the collision of a soccer ball with the eye to better understand the pathophysiology of observed ocular and retinal injuries and to compare them with those observed in abusive head trauma (AHT).Computer simulation study.None.A finite element model of the eye was used to investigate the effects of a collision of a soccer ball on the eye.Intraocular pressure and stress.Impact of the soccer ball with the eye generated a pressure wave that traveled through the vitreous, creating transient pockets of high and negative pressure. During the high-frequency phase, pressure in the vitreous near the posterior pole ranged from 39.6 to -30.9 kPa. Stress in ocular tissue was greatest near the point of contact, with a peak of 66.6 kPa. The retina experienced the greatest stress at the vasculature, especially at distal branches, where stress rose to 15.4 kPa. On average, retinal stress was greatest in the subretinal layer, but was highest in the preretinal layer when considering only vascular tissue.The high intraocular pressure and stress in ocular tissue near the point of soccer ball impact suggest that injuries to the anterior segment of the eye can be attributed to direct transmission of force from the ball. The subsequent propagation of a pressure wave may cause injuries to the posterior segment as the positive and negative pressures exert compressive and tractional forces on the retina. The linear movement of the pressure wave likely accounts for localization of retinal lesions to the posterior pole or superior temporal quadrant. The primarily linear force in soccer ball trauma is the probable cause for the more localized injury profile and lower retinal hemorrhage incidence compared with AHT, in which repetitive angular force is also at play. 

http://www.ophthalmologyscience.org/article/S2666914522000185/pdf

Finite Element Analysis of Soccer Ball-Related Ocular and Retinal Trauma and Comparison with Abusive Head Trauma

The invention discloses a clamping device of a Hopkinson pull bar test-piece and an experimental method and belongs to the field of shock dynamics experiment. The experimental device is used in pairs. One end of an adapter is in threaded connection with an incident bar or transmission bar, and the threaded clearance is filled with thread seal tape so as to avoid the damage of shock wave to connecting thread; and the other end of the adapter is provided with a square groove to be connected to a flat test-piece. The square groove which matches the test-piece undergoes plane machining into tiny serrated teeth so as to increase frictional force during clamping. The outer rim of the adapter is processed into taper thread which matches a nut. When the clamping device is in use, clamping force perpendicular to the groove surface is provided by screwing-in the nut. According to the invention, the problem that screw thread is not easy to process in a composite material and high-strength glue is nonuniform during gluing process can be greatly avoided, connection type of a fibrous composite material under dynamic tension is studied, and a forceful foundation is laid for the constitutive relation of the fibrous composite material under dynamic tension.

Clamping device of Hopkinson pull bar test-piece and experimental method

BACKGROUND Careful evaluation of the risk of stent under-expansions before the intervention will aid treatment planning, including the application of a pre-stent plaque modification strategy. OBJECTIVES It remains challenging to achieve a proper stent expansion in the presence of severely calcified coronary lesions. Building on our work in deep learning segmentation, we created an automated machine learning approach that uses lesion attributes to predict stent under-expansion from pre-stent images, suggesting the need for plaque modification. METHODS Pre- and post-stent intravascular optical coherence tomography image data were obtained from 110 coronary lesions. Lumen and

Pengfei Dong

Papers

Optimization of Freeze-FRESH Methodology for 3D Printing of Microporous Collagen Constructs

Serum Homocysteine Level Predictive Capability for Severity of Restenosis Post Percutaneous Coronary Intervention

Finite Element Analysis of Soccer Ball-Related Ocular and Retinal Trauma and Comparison with Abusive Head Trauma

Clamping device of Hopkinson pull bar test-piece and experimental method

Prediction of stent under-expansion in calcified coronary arteries using machine-learning on intravascular optical coherence tomography