A virtual laboratory system for physiology teaching

The problem of understanding physiological processes can be aided by visualization tools. Traditionally this has been achieved by the use of schematic paper diagrams. However, many physiological processes are quite complex, and in many instances students encounter difficulties in understanding the dynamics. This paper describes the rationale behind an alternative approach using interactive three‐dimensional computer‐graphics simulation to aid comprehension of scientific concepts

Oxidation and creep behavior of Mo5Si3 based materials

Mo[subscript]5 Si[subscript]3 shows promise as a high temperature creep resistant material. The high temperature oxidation resistance of Mo[subscript]5 Si[subscript]3 has been found to be poor, however, limiting its use in oxidizing atmospheres. Mo [subscript]5Si[subscript]3 exhibits mass loss during oxidation at 800°-1200° C due to volatilization of molybdenum oxide, indicating that the silica scale that forms does not provide a passivating layer. Catastrophic \u27pest\u27 oxidation occurs at 800° C. The oxidation rate at 1200° C is on the order of 10[superscript]3 mg cm[superscript]-2 hr[superscript]-1. The addition of boron results in protective scale formation and parabolic oxidation kinetics in the temperature range of 1050°-1300° C. The oxidation rate of Mo[subscript]5 Si[subscript]3 was decreased by 5 orders of magnitude at 1200° C by doping with less than two weight percent boron. Boron doping eliminates catastrophic \u27pest\u27 oxidation at 800° C. Oxidation and scale formation on several Mo[subscript]5 Si[subscript]3 based Mo-Si-B multiphase intermetallics was studied at 600° C-1300° C using SEM, XRD, ESCA, and thermogravimetric analysis. The mechanism for the improvement in oxidation resistance was found to be scale modification by boron. Boron additions of as low as 0.14 wt% promote formation of a passivating scale by allowing viscous flow to occur;The compressive creep rate of an MoSi[subscript]3 based Mo-Si-B composition was evaluated at 1240°-1320° C and 140-180 MPa. The composition tested had a three phase microstructure composed of Mo[subscript]5 Si[subscript]3 (T1), Mo[subscript]3Si, and a ternary Mo[subscript]5( Si,B)[subscript]3 (T2) phase. The average creep stress exponent and activation energy were found to be n = 4.3 and E[subscript] a = 396 kJ/mol. The boron modified Mo[subscript]5 Si[subscript]3 was found to have approximately the same creep rate as Mo[subscript]5 Si[subscript]3 at 140 MPa. TEM analysis of the crept microstructure of the boron modified material reveals no evidence for dislocation activity in T1. Only basal slip was observed in the T2 phase. \001 dislocations and polygonal subgrain structures were observed in Mo[subscript]3 Si. Mo[subscript]3 Si and T2 were found to stop cracks that nucleate in the T1 phase during creep

The Inferred Cardiogenic Gene Regulatory Network in the Mammalian Heart

Cardiac development is a complex, multiscale process encompassing cell fate adoption, differentiation and morphogenesis. To elucidate pathways underlying this process, a recently developed algorithm to reverse engineer gene regulatory networks was applied to time-course microarray data obtained from the developing mouse heart. Approximately 200 genes of interest were input into the algorithm to generate putative network topologies that are capable of explaining the experimental data via model simulation. To cull specious network interactions, thousands of putative networks are merged and filtered to generate scale-free, hierarchical networks that are statistically significant and biologically relevant. The networks are validated with known gene interactions and used to predict regulatory pathways important for the developing mammalian heart. Area under the precision-recall curve and receiver operator characteristic curve are 9% and 58%, respectively. Of the top 10 ranked predicted interactions, 4 have already been validated. The algorithm is further tested using a network enriched with known interactions and another depleted of them. The inferred networks contained more interactions for the enriched network versus the depleted network. In all test cases, maximum performance of the algorithm was achieved when the purely data-driven method of network inference was combined with a data-independent, functional-based association method. Lastly, the network generated from the list of approximately 200 genes of interest was expanded using gene-profile uniqueness metrics to include approximately 900 additional known mouse genes and to form the most likely cardiogenic gene regulatory network. The resultant network supports known regulatory interactions and contains several novel cardiogenic regulatory interactions. The method outlined herein provides an informative approach to network inference and leads to clear testable hypotheses related to gene regulation

Tomographic Imaging of Traveling Ionospheric Disturbances Using GNSS and Geostationary Satellite Observations

Abstract Traveling ionospheric disturbances (TIDs) are the manifestations of atmospheric gravity waves in the ionosphere. These disturbances have practical importance because they affect satellite navigation technologies such as Global Navigational Satellite System (GNSS), causing degradation in precise positioning applications. They also have scientific significance as their generation mechanisms and propagation are not fully understood. While there are specific instruments that can measure TIDs in certain locations, there is a need for wide-area observations across extended geographical regions to continuously monitor their onset and spatial and temporal characteristics. This paper evaluates the use of observations from ground-based geodetic GNSS receivers to image TIDs using ionospheric tomography and data assimilation. Certain GNSS receivers also monitor signals from geostationary (GEO) satellites, which provide a unique perspective on the TID. The advantage of using the GEO data is investigated. A computerized simulation of GNSS observations is used for evaluation of the Multi-Instrument Data Analysis System (MIDAS) with GEO and regular GNSS geometry. The simulated observations are generated by integrating the electron density through a modeled TID-perturbed dynamic ionosphere between actual receiver and satellite positions. The output 3-D electron density image series generated from the synthetic data by the MIDAS ionospheric tomography and data assimilation algorithm are compared with the input model ionosphere. Results show that GEO geometry improves the reconstruction of medium-scale TIDs (MSTIDs) and smaller LSTIDs in cases where the movement of regular GNSS satellites in Medium Earth orbit (MEO) may otherwise introduce distortions to the observations

PERISCOPE: PERIapsis Subsurface Cave Optical Explorer

The PERISCOPE study focuses primarily on lunar caves, due to the potential for being imaged in orbital scenarios. In the intervening years, from 2012-2015, scientists developed further rationales and interest in the scientific value of lunar caves. It does not appear that they are likely to be sinks for water-ice due to the relatively warm temperatures(~-20 degrees Celsius) in the caves leading to geologically-rapid migration of unbound water due to sublimation, and inevitable loss through any skylights. However, the skylights themselves reveal apparent complex layering, which may speak to a more complex multi-stage evolution of mare flood basalts than previously considered, and so their examination may provide even more insight into the lunar mare, which in turn provide a primary record of early solar system crustal formal and evolution processes. Further extrapolation of these insights can be found within the exoplanet community of researchers,who find the information useful for calibrating star formation and planetary evolution models. In addition, catalogues of lunar and martian skylights, "caves" or "atypical pit craters" have been developed, with numbers for both bodies now in the low hundreds thanks to additional high resolution surveys and revisiting the existing image databases

Activin-A and Bmp4 Levels Modulate Cell Type Specification during CHIR-Induced Cardiomyogenesis

The use of human pluripotent cell progeny for cardiac disease modeling, drug testing and therapeutics requires the ability to efficiently induce pluripotent cells into the cardiomyogenic lineage. Although direct activation of the Activin-A and/or Bmp pathways with growth factors yields context-dependent success, recent studies have shown that induction of Wnt signaling using low molecular weight molecules such as CHIR, which in turn induces the Activin-A and Bmp pathways, is widely effective. To further enhance the reproducibility of CHIR-induced cardiomyogenesis, and to ultimately promote myocyte maturation, we are using exogenous growth factors to optimize cardiomyogenic signaling downstream of CHIR induction. As indicated by RNA-seq, induction with CHIR during Day 1 (Days 0–1) was followed by immediate expression of Nodal ligands and receptors, followed later by Bmp ligands and receptors. Co-induction with CHIR and high levels of the Nodal mimetic Activin-A (50–100 ng/ml) during Day 0–1 efficiently induced definitive endoderm, whereas CHIR supplemented with Activin-A at low levels (10 ng/ml) consistently improved cardiomyogenic efficiency, even when CHIR alone was ineffective. Moreover, co-induction using CHIR and low levels of Activin-A apparently increased the rate of cardiomyogenesis, as indicated by the initial appearance of rhythmically beating cells by Day 6 instead of Day 8. By contrast, co-induction with CHIR plus low levels (3–10 ng/ml) of Bmp4 during Day 0–1 consistently and strongly inhibited cardiomyogenesis. These findings, which demonstrate that cardiomyogenic efficacy is improved by optimizing levels of CHIR-induced growth factors when applied in accord with their sequence of endogenous expression, are consistent with the idea that Nodal (Activin-A) levels toggle the entry of cells into the endodermal or mesodermal lineages, while Bmp levels regulate subsequent allocation into mesodermal cell types

Towards Untethered Soft Robots Driven By Electrohydraulic Artificial Muscles

As humans, we are continually integrating technology into our everyday lives. From wearable smart watches to autonomous vacuum cleaners, modern day machines are steadily moving out of warehouses and factories and into our homes to enhance our lifestyles. In doing so, there is an ever-growing need for machines that can safely operate in extremely diverse or unpredictable environments, which often includes collaborative spaces near humans. This requirement presents challenges for traditional robots that commonly employ rigid architectures driven by heavy motors, gears, and linkages, which rely on precise computation of the state at each degree of freedom to safely function. Moreover, the underlying mechanics of these modern-day robotic architectures are fundamentally different than those which have evolved naturally; biological organisms exploit a host of compliant, robust, and multifunctional structures that tightly integrate actuation, sensing, and control. These biological structures, in animals for instance, enable feats of strength, agility, and autonomy that are currently impossible for human-made robots. A paradigm shift in robotic design and implementation is required for the next generation of machines. This approach will reinvent the idea of a robot, moving from a rigid block design to a soft continuum that integrates lightweight, compliant, and versatile components. While this approach will require multi-disciplinary advances in material science, control theory, and engineering, a fundamental component of these machines will ultimately be the actuators that drive them. Thus, researchers and engineers are developing soft actuators that mimic the strength, speed, and scalability of natural muscle. These bio-inspired components could unlock a multitude of applications for machines, and even blur the lines between science and science fiction. For example, soft wearable robots can provide haptic feedback for an immersive virtual reality experience, ultra-adaptable soft robotic cephalopods could explore marine environments to conduct research and reconnaissance, while highly resilient space robots could explore extraterrestrial environments to uncover the origins of life. This dissertation is focused on a novel type of soft actuator (or artificial muscle) called a Hydraulically Amplified Self-healing ELectrostatic (HASEL) actuator, and its application to soft robotics devices. The first chapter will explore the state-of-the-art in soft robotics technologies, with a focus on soft actuation. The second chapter will elucidate the fundamentals of HASEL actuators and their application to soft robotic technologies. The third chapter will detail a toolkit based on off-the-shelf-materials that can be used to prototype, fabricate, power, and test HASEL actuators. This chapter will detail exemplary designs of HASEL, their modes of actuation and performance, as well as their application to soft-robotic devices such as a continuum robot capable of grasping and manipulating delicate objects. Continuing to the fourth chapter, a novel design for a linearly contractile actuator is presented, characterized on both an experimental and theoretical basis, and then demonstrated as a soft tubular pump. In the fifth chapter, we develop a state-of-the-art 10-channel high voltage power supply to independently control groups of HASEL actuators. This power supply features a compact form-factor that is about the size of a standard smart phone. Next, chapter six will focus on soft robots for space exploration. A feasibility study details a robot design for asteroid mining, and initial prototypes are discussed with a focus on electrohydraulic actuation and electrostatic adhesion mechanisms for robot locomotion and grappling. Finally, chapter seven concludes the dissertation with a summary of the developments presented here, while also laying the framework for future studies.</p

Modelling the transfer function of two-dimensional SQUID and SQIF arrays with thermal noise

We present a theoretical model for 2D SQUID and SQIF arrays with over-damped Josephson junctions for uniform bias current injection at 77 K. Our simulations demonstrate the importance of including Johnson thermal noise and reveal that the mutual inductive coupling between SQUID loops is of minor importance. Our numerical results establish the validity of a simple scaling behaviour between the voltages of 1D and 2D SQUID arrays and show that the same scaling behaviour applies to the maximum transfer functions. The maximum transfer function of a 2D SQUID array can be further optimised by applying the optimal bias current which depends on the SQUID loop self-inductance and the junction critical current. Our investigation further reveals that a scaling behaviour exits between the maximum transfer function of a 2D SQUID array and that of a single dc-SQUID. Finally, we investigate the voltage response of 1D and 2D SQIF arrays and illustrate the effects of adding spreads in the heights and widths of SQUID loops.Comment: 9 Figures Submitted to PR

Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

Impact of \u3cem\u3eMYH6\u3c/em\u3e Variants in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P \u3c 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P \u3c 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P \u3c 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P \u3c 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications