Search for: All records

In tissues and organs, the extracellular matrix (ECM) helps maintain inter- and intracellular architectures that sustain the structure–function relationships defining physiological homeostasis. Combining fiber scaffolds and cells to form engineered tissues is a means of replicating these relationships. Engineered tissues' fiber scaffolds are designed to mimic the topology and chemical composition of the ECM network. Here, we asked how cells found in the heart compare in their propensity to align their cytoskeleton and self-organize in response to topological cues in fibrous scaffolds. We studied cardiomyocytes, valvular interstitial cells, and vascular endothelial cells as they adapted their inter- and intracellular architectures to the extracellular space. We used focused rotary jet spinning to manufacture aligned fibrous scaffolds to mimic the length scale and three-dimensional (3D) nature of the native ECM in the muscular, valvular, and vascular tissues of the heart. The representative cardiovascular cell types were seeded onto fiber scaffolds and infiltrated the fibrous network. We measured different cell types' propensity for cytoskeletal alignment in response to fiber scaffolds with differing levels of anisotropy. The results indicated that valvular interstitial cells on moderately anisotropic substrates have a higher propensity for cytoskeletal alignment than cardiomyocytes and vascular endothelial cells. However, all cell types displayed similar levels of alignment on more extreme (isotropic and highly anisotropic) fiber scaffold organizations. These data suggest that in the hierarchy of signals that dictate the spatiotemporal organization of a tissue, geometric cues within the ECM and cellular networks may homogenize behaviors across cell populations and demographics.

 

Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol–gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties. 

Pediatric heart valve disease affects children worldwide and necessitates valve replacements that remodel and grow with the patient. Current valve manufacturing technologies struggle to create valves that facilitate native tissue remodeling for permanent replacements. Here, we present focused rotary jet spinning (FRJS) for implantable medical devices, such as heart valves, to address this challenge. Combining RJS and a focused air stream, FRJS prints FibraValves, micro- and nanofibrous heart valves, in minutes. The micro- and nanoscale features provide structural cues to orient cells at the biotic-abiotic interface, while the centimeter-scale valve shape regulates cardiac flow. We built valves using poly(L-lactide-co-Ɛ-caprolactone) fiber scaffolds, which supported rapid cellular infiltration and displayed native valve-like mechanical properties. Evaluating clinical translatability, we assessed acute performance in a large animal model using a transcatheter delivery approach. These tests indicate that FRJS is a viable method for manufacturing heart valves and future medical implants. 

Food waste and food safety motivate the need for improved food packaging solutions. However, current films/coatings addressing these issues are often limited by inefficient release dynamics that require large quantities of active ingredients. Here we developed antimicrobial pullulan fibre (APF)-based packaging that is biodegradable and capable of wrapping food substrates, increasing their longevity and enhancing their safety. APFs were spun using a high-throughput system, termed focused rotary jet spinning, with water as the only solvent, allowing the incorporation of naturally derived antimicrobial agents. Using avocados as a representative example, we demonstrate that APF-coated samples had their shelf life extended by inhibited proliferation of natural microflora, and lost less weight than uncoated control samples. This work offers a promising technique to produce scalable, low-cost and environmentally friendly biodegradable antimicrobial packaging systems. 

Helical alignments within the heart’s musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart’s musculature using current techniques. Here we report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.

 

sPHENIX is a high energy nuclear physics experiment under construction at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory (BNL). The primary physics goals of sPHENIX are to study the quark-gluon-plasma, as well as the partonic structure of protons and nuclei, by measuring jets, their substructure, and heavy flavor hadrons in$$p$$$p$$$+$$$+$$$p$$$p$,p+ Au, and Au + Au collisions. sPHENIX will collect approximately 300 PB of data over three run periods, to be analyzed using available computing resources at BNL; thus, performing track reconstruction in a timely manner is a challenge due to the high occupancy of heavy ion collision events. The sPHENIX experiment has recently implemented the A Common Tracking Software (ACTS) track reconstruction toolkit with the goal of reconstructing tracks with high efficiency and within a computational budget of 5 s per minimum bias event. This paper reports the performance status of ACTS as the default track fitting tool within sPHENIX, including discussion of the first implementation of a time projection chamber geometry within ACTS.

 

Delegating managerial tasks is essential for firm growth. Most firms in developing countries, however, do not hire outside managers but instead rely on family members. In this paper, we ask if this lack of managerial delegation can explain why firms in poor countries are small and whether it has important aggregate consequences. We construct a model of firm growth where entrepreneurs have a fixed time endowment to run their daily operations. As firms grow large, the need to hire outside managers increases. Firms’ willingness to expand therefore depends on the ease with which delegation can take place. We calibrate the model to plant-level data from the United States and India. We identify the key parameters of our theory by targeting the experimental evidence on the effect of managerial practices on firm performance from Bloom et al. (2013). We find that inefficiencies in the delegation environment account for 11 percent of the income per capita difference between the United States and India. They also contribute to the small size of Indian producers, but would cause substantially more harm for US firms. The reason is that US firms are larger on average and managerial delegation is especially valuable for large firms, thus making delegation efficiency and other factors affecting firm growth complements. (JEL D22, G32, L25, L26, O14) 

The locations of proton-proton collision points in LHC experiments are called primary vertices (PVs). Preliminary results of a hybrid deep learning algorithm for identifying and locating these, targeting the Run 3 incarnation of LHCb, have been described at conferences in 2019 and 2020. In the past year we have made significant progress in a variety of related areas. Using two newer Kernel Density Estimators (KDEs) as input feature sets improves the fidelity of the models, as does using full LHCb simulation rather than the “toy Monte Carlo” originally (and still) used to develop models. We have also built a deep learning model to calculate the KDEs from track information. Connecting a tracks-to-KDE model to a KDE-to-hists model used to find PVs provides a proof-of-concept that a single deep learning model can use track information to find PVs with high efficiency and high fidelity. We have studied a variety of models systematically to understand how variations in their architectures affect performance. While the studies reported here are specific to the LHCb geometry and operating conditions, the results suggest that the same approach could be used by the ATLAS and CMS experiments. 

Hemogen is a vertebrate transcription factor that performs important functions in erythropoiesis and testicular development and may contribute to neoplasia. Here we identify zebrafish Hemogen and show that it is considerably smaller (∼22 kDa) than its human ortholog (∼55 kDa), a striking difference that is explained by an underlying modular structure. We demonstrate that Hemogens are largely composed of 21-25 amino acid repeats, some of which may function as transactivation domains (TADs). Hemogen expression in embryonic and adult zebrafish is detected in hematopoietic, renal, neural, and gonadal tissues. Using Tol2- and CRISPR/Cas9-generated transgenic zebrafish, we show that Hemogen expression is controlled by two Gata1-dependent regulatory sequences that act alone and together to control spatial and temporal expression during development. Partial depletion of Hemogen in embryos by morpholino knock-down reduces the number of erythrocytes in circulation. CRISPR/Cas9-generated zebrafish lines containing either a frameshift mutation or an in-frame deletion in a putative, C-terminal TAD display anemia and embryonic tail defects. This work expands our understanding of Hemogen and provides mutant zebrafish lines for future study of the mechanism of this important transcription factor.