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Radiation therapy (RT) is essential to managing many pediatric malignancies but can provoke anxiety, fear, and discomfort for children owing to prolonged treatment time, extended course, and restrictive immobilization. Patients younger than 10 years frequently require daily general anesthesia (GA), which is resource intensive, expensive, potentially toxic, and anxiety and fear provoking. Audio-Visual Assisted Therapeutic Ambience in Radiation Therapy (AVATAR), a video streaming device, has been proposed as an alternative to anesthesia in patients aged 3 to 10 years. A pilot study evaluating the efficacy of this novel innovation is accruing, but patients younger than 3 years are ineligible.We simulated a 2-year-old with stage IV Wilms tumor for bilateral whole-lung and left-flank irradiation without GA. Using AVATAR, we attempted to deliver RT to this patient without sedation. Patient anxiety at the time of simulation and at the beginning, middle, and end of the treatment course was characterized using the validated Modified Yale Preoperative Anxiety Score (mYPAS) measurement tool.Although the patient tolerated computed tomography simulation without GA or AVATAR use, his mYPAS of 14 out of 18 indicated significant anxiety. Using AVATAR, all treatments were delivered without GA; his mYPASs were 5 and 4 (the lowest possible) and 4 at the first, midcourse, and final treatments, indicating no significant anxiety and a decrease from the pre-AVATAR baseline. Without GA, the time to deliver RT decreased by 66% from 90 to 30 minutes.We describe an expanded, previously unreported indication for AVATAR by demonstrating the feasibility of this approach to reduce or omit anesthesia in appropriate younger patients currently excluded from ongoing trials. The financial and quality-of-life benefits (including decreased stress, anxiety, toxic effects, cost, and appointment time) of AVATAR use may be extendable to a younger patient population than previously thought. In older children, prospective validation is ongoing, but additional study in patients younger than 3 years is needed.

Although controlled radical polymerization is an excellent tool to make precision polymeric materials, reversal of the process to retrieve the starting monomer is far less explored despite the significance of chemical recycling. Current depolymerization approaches typically require elevated temperatures (>350 ˚C), high dilutions in specific solvents (typically 0.1-25 mM polymer concentrations), and/or expensive catalysts. Here, we report that RAFT-synthesized polymers can undergo a low-temperature solvent-free depolymerization back to monomer thanks to the partial in-situ transformation of the RAFT end-group to macromonomer. To aid a more complete depolymerization, we performed a facile and quantitative end-group modification strategy with the modified RAFT polymers exhibiting significantly higher depolymerization conversions (~90%) at comparable temperatures. The end-group transformation was applied to polymers synthesized by ATRP triggering an efficient low-temperature bulk depolymerization (~90% of monomer regeneration) with an onset at 150 ˚C, in contrast to previous reports where depolymerization could only be triggered at much higher temperatures (> 350 ˚C). The versatility of the methodology was demonstrated by a scalable depolymerization (~10 g of starting polymer) retrieving 84% yield of the starting monomer intact which could be subsequently used for further polymerization. This work presents a new low-energy approach for depolymerizing controlled radical polymers and creates many future opportunities as high-yielding, solvent-free and scalable depolymerization methods are sought.

SUMMARYB-cell lineage acute lymphoblastic leukemia (B-ALL) is comprised of diverse molecular subtypes and while transcriptional and DNA methylation profiling of B-ALL subtypes has been extensively examined, the accompanying chromatin landscape is not well characterized for many subtypes. We therefore mapped chromatin accessibility using ATAC-seq for 10 B-ALL molecular subtypes in primary ALL cells from 154 patients. Comparisons with B-cell progenitors identified candidate B-ALL cell-of-origin and AP-1-associatedcis-regulatory rewiring in B-ALL.Cis-regulatory rewiring promoted B-ALL-specific gene regulatory networks impacting oncogenic signaling pathways that perturb normal B-cell development. We also identified that over 20% of B-ALL accessible chromatin sites exhibit strong subtype enrichment, with transcription factor (TF) footprint profiling identifying candidate TFs that maintain subtype-specific chromatin architectures. Over 9000 inherited genetic variants were further uncovered that contribute to variability in chromatin accessibility among individual patient samples. Overall, our data suggest that distinct chromatin architectures are driven by diverse TFs and inherited genetic variants which promote unique gene regulatory networks that contribute to transcriptional differences among B-ALL subtypes.HIGHLIGHTSPro-B progenitor cells as the most common cell-of-origin for B-ALLAP-1 TF-associatedcis-regulatory rewiring in B-ALLSubtype-specific accessible chromatin signatures representing 20% of all B-ALL sitesRole for distinct TFs in promoting subtype-specific chromatin architecturesThousands of inherited genetic variants identified impacting chromatin state

The etiology of neurodegenerative diseases is poorly understood; however, studies have shown that heavy metals, such as copper, play a critical role in neurotoxicity, thus, adversely affecting the development of these diseases. Because of the limitations associated with classical metal detection tools to obtain accurate speciation information of ultra-low concentrations of heavy metals in the brain, analysis is primarily performed in blood, urine, or postmortem tissues, limiting the translatability of acquired knowledge to living systems. Inadequate and less accurate data obtained with such techniques provide little or no information for developing efficient therapeutics that aid in slowing down the deterioration of brain cells. In this study, we developed a biocompatible, ultra-fast, low-cost, and robust surface-modified electrode with carbon fibers by electrodepositing dopamine via fast-scan cyclic voltammetry (FSCV) to detect Cu

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by fibro-fatty infiltration with an increased propensity for ventricular arrhythmias and sudden death. Genetic variants in desmosomal genes are associated with ACM. Incomplete penetrance is a common feature in ACM families, complicating the understanding of how external stressors contribute towards disease development. To analyze the dual role of genetics and external stressors on ACM progression, we developed one of the first mouse models of ACM that recapitulates a human variant by introducing the murine equivalent of the human R451G variant into endogenous desmoplakin (

Trithiol chelates are suitable for labeling radioarsenic (72As: 2.49 MeV β+, 26 h; 77As: 0.683 MeV β-, 38.8 h) to form potential theranostic radiopharmaceuticals for positron emission tomography (PET) imaging and therapy. A trithiol(b)-(Ser)2-RM2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol(b)-(Ser)2-RM2 bioconjugate was radiolabeled with no-carrier-added 77As in over 95% radiochemical yield and was stable for over 48 h, and in vitro IC50 cell binding studies of [77As]As-trithiol(b)-(Ser)2-RM2 in PC-3 cells demonstrated high affinity for the gastrin-releasing peptide (GRP) receptor (low nanomolar range). Limited biodistribution studies in normal mice were performed with HPLC purified 77As-trithiol(b)-(Ser)2-RM2 demonstrating both pancreatic uptake and hepatobiliary clearance.

ObjectiveChildren diagnosed with cancer experience stress associated with their diagnosis and treatment and are at heightened risk for problems in social adjustment. This study investigated the association between coping with cancer-related stress and problems in social adjustment across the first year after a pediatric cancer diagnosis.MethodsMothers of children (ages 5–17 years) with cancer (N = 312) were recruited from two children’s hospitals. Mother’s reported on their child’s social adjustment and coping near diagnosis (T1) and 12 months (T2).ResultsPrimary, secondary control, and disengagement coping were significantly associated with concurrent social adjustment at 12 months. The bivariate associations between baseline primary and secondary control coping and social problems 12 months later were no longer significant in a multivariate regression model.ConclusionsThese findings inform our understanding of the association between coping with cancer-related stress and social adjustment of children diagnosed with cancer. Interventions teaching primary and secondary control coping strategies for cancer-related stressors may offer some benefit to concurrent youth social adjustment. Further research is needed on how best to support social adjustment in this population over time.

Zonula occludens-1 (ZO-1) is an intracellular scaffolding protein that orchestrates the anchoring of membrane proteins to the cytoskeleton in epithelial and specialized tissue including the heart. There is clear evidence to support the central role of intracellular auxiliary proteins in arrhythmogenesis and previous studies have found altered ZO-1 expression associated with atrioventricular conduction abnormalities. Here, using human cardiac tissues, we identified all three isoforms of ZO-1, canonical (Transcript Variant 1

Autonomous vehicle control approaches are rapidly being developed for everyday street-driving scenarios. This article considers autonomous vehicle control in a less common, albeit important, situation “a vehicle stuck in a ditch.” In this scenario, a solution is typically obtained by either using a tow-truck or by humans rocking the vehicle to build momentum and push the vehicle out. However, it would be much more safe and convenient if a vehicle was able to exit the ditch autonomously without human intervention. In exploration of this idea, this article derives the governing equations for a vehicle moving along an arbitrary ditch profile with torques applied to front and rear wheels and the consideration of four regions of wheel-slip. A reward function was designed to minimize wheel-slip, and the model was used to train control agents using Probabilistic Inference for Learning COntrol (PILCO) and deep deterministic policy gradient (DDPG) reinforcement learning (RL) algorithms. Both rear-wheel-drive (RWD) and all-wheel-drive (AWD) results were compared, showing the capability of the agents to achieve escape from a ditch while minimizing wheel-slip for several ditch profiles. The policy results from applying RL to this problem intuitively increased the momentum of the vehicle and applied “braking” to the wheels when slip was detected so as to achieve a safe exit from the ditch. The conclusions show a pathway to apply aspects of this article to specific vehicles.

The Full Law Analysis Scattering System Hub (FLASSH) is an advanced code which evaluates the thermal scattering law (i.e. TSL, S(α,β)) for thermal scattering cross sections and resonance Doppler broadening. The ability to accurately capture these two key cross section features is dependent on accurate, high fidelity TSL evaluations. FLASSH 1.0 provides advanced physics capabilities resulting in an improved, generalized TSL to most accurately represent the lattice dynamics within any material. This improved TSL will allow for consistent analysis in both the thermal and epithermal energy ranges. The features for TSL analysis are packaged within the FLASSH GUI for easy user interface along with data output in many file formats including ENDF File 7 and ACE files.

The current study examined whether associations between functions of aggression (proactive and reactive) and peer victimization (physical and relational) were moderated by parental psychological control in a sample of elementary school-aged children. Analyses were based on a sample of 279 children in grades three through five. Data was collected in the fall and spring of a single academic year. Peer victimization was assessed through child- and teacher-report, and functions of aggression and parental psychological control were measured through child-report. Multiple group models, with student sex as the grouping variable, were estimated to address study hypotheses. Findings from multiple group path models revealed significant effects for boys only. For boys who reported a high level of parental psychological control, proactive aggression was a negative predictor of child-reported physical victimization. Additionally, parental psychological control moderated the association between boys’ reactive aggression and teacher-reported relational victimization. At low levels of parental psychological control, reactive aggression was a positive predictor of relational victimization whereas reactive aggression was a negative predictor of peer victimization at high levels of psychological control. Our results suggest that for boys who endorse a high level of parental psychological control, aggression is negatively associated with peer victimization. We argue that children who experience a high level of parental psychological control are more likely to apply those same strategies in their peer relationships, which makes them less likely to be targets of relational and physical victimization. This study helps inform our understanding of the role of parental psychological control in the relation between aggression and peer relationship difficulties.

The authors examined perceptions of key social cognitive career theory (Lent, Brown, & Hackett, 1994) variables related to college-going and science, technology, engineering, math, and medical (STEMM) careers in 10th and 11th graders (N = 892) attending 3 rural Appalachian high schools. The authors examined differences in perceptions related to gender, prospective 1st-generation college student status, and the presence or absence of aspirations to pursue a STEMM career. Young women and young men scored similarly on all but 1 dependent variable, college-going self-efficacy (young women scored higher). Students who had STEMM career aspirations had higher scores on every measure than those who did not. Results suggest examining a 3rd prospective 1st-generation college student status group—students who are unsure of their parents’ education level—as a distinct group in future research. By examining the college-going and STEMM attitudes of rural Appalachian high school students, this study advances the literature and informs practitioners on reducing educational and vocational inequalities in this region.

A Vaiṣṇava Poet in Early Modern Bengal: Kavikarṇapūra’s Splendour of Speech. By Rembert Lutjeharms. Oxford Theology and Religion Monographs. Oxford: Oxford University Press, 2018. Pp. 360. $99.

Social cognitive career theory indicates that perceived barriers negatively affect career and educational self-efficacy beliefs and may also impact interests, goals, and actions. However, measurement of barriers has produced mixed results, and few quantitative studies explore the perceived barriers of rural Appalachian students. In this series of studies, we explored the perceived educational and career barriers of rural Appalachian high school students. Our goal was to identify perceived barriers, but as initial results were analyzed, we then shifted to how best to measure barriers and how culture impacted the reporting of barriers by rural Appalachian students. The results of our mixed-method series of studies offer ideas on how cultural values and beliefs may skew reporting of contextual influences on career and education.

Base oil lubricants are prevalent in many mechanical systems and can have a wide range of chemical compositions. Their carbon numbers generally span from C20–40, and they are often classified by their predominant molecular species (e.g., paraffinic, naphthenic). These heavy, viscous fluids are of interest when used in or around nuclear fuel cycle facilities, where they may influence the local neutronic environment. Furthermore, variations in molecular structure impact the oil’s dynamic properties and render the modeling process a challenging endeavor. In this work, a model for a specific paraffinic oil was developed for obtaining the vibrational/translational density of states (DOS) for hydrogen and carbon, the primary and secondary scattering species, respectively. The DOS was subsequently used to generate the thermal scattering law (TSL). The molecular ensemble, constructed using the MedeA material design platform, was benchmarked using available static and dynamic properties (i.e., density, viscosity, viscosity index, diffusivity). All simulations were performed using the LAMMPS code, and the COMPASS force field, a semi-empirical molecular potential, was selected as a suitable representation of the system dynamics. Additionally, a modified version of the nuclear data processing code, NJOY, was employed to more accurately treat a viscous fluid. Through this investigation, the viscous behavior characteristic of a heavy paraffinic oil was captured and was found to minimally impact the TSL when compared to the solid approximation.

Drum brakes have dominated the braking industry for many years and will most likely continue to do so for the foreseeable future due to their low cost and adequate operating performance. Basic equations for conventional brake are presented, while complicated analysis has been published using finite element methods to predict brake squeal and instability. This paper seeks to step away from the complexity of numerical models to consider the fundamental braking phenomenon of a single-shoe drum brake, using nondimensional, closed-form analysis and a Taylor series expansion to examine the effects of perturbing dimensionless design parameters. In addition, an optimal design for the conventional brake is achieved using Taguchi method. In conclusion, this paper shows that the braking torque is dependent upon only four dimensionless groups, and that two of these groups dominate the physics of braking. Furthermore, it is shown that adjustments to these two dominating groups have a direct impact on the contact pressure between that shoe material and the brake drum, and that this pressure must be kept below the yield strength of the braking material in order to prevent a mechanical failure of the brake. Since the results are nondimensional, they are generally applicable to all single-shoe drum brakes having a design with mechanical features that are similar to the one analyzed in this paper. There is very good agreement between the results of both Taguchi and sensitivity regarding the significance and insignificance of the design parameters.

Desmoplakin (DSP) is a large (~260 kDa) protein found in the desmosome, a subcellular complex that links the cytoskeleton of one cell to its neighbor. A mutation ‘hot-spot’ within the NH2-terminal third of the DSP protein (specifically, residues 299–515) is associated with both cardiomyopathies and skin defects. In select DSP variants, disease is linked specifically to the uncovering of a previously-occluded calpain target site (residues 447–451). Here, we partially stabilize these calpain-sensitive DSP clinical variants through the addition of a secondary single point mutation—tyrosine for leucine at amino acid position 518 (L518Y). Molecular dynamic (MD) simulations and enzymatic assays reveal that this stabilizing mutation partially blocks access to the calpain target site, resulting in restored DSP protein levels. This ‘molecular band-aid’ provides a novel way to maintain DSP protein levels, which may lead to new strategies for treating this subset of DSP-related disorders.

Trithiol chelates are suitable for labeling radioarsenic (

We examined associations between proactive and reactive aggression and peer likability across two academic years. Analyses were based on a sample of 442 elementary school children. Proactive and reactive aggression were assessed through self-report and peer likability was assessed via a peer nomination inventory. Data were collected in the fall and spring of two academic years. Findings from cross-lagged multiple group longitudinal panel models where pathways were freely estimated for boys and girls provided evidence that the relation between reactive aggression and reciprocated liking and received only liking nominations was negative and transactional for girls. Proactive aggression had mixed associations with likability between boys and girls. Our findings suggest that preventative interventions that focus on reducing reactive aggression or increasing peer likability have the potential to shift children away from trajectories of long-term maladjustment.

Zonula occludens-1 (ZO-1) is an intracellular scaffolding protein that orchestrates the anchoring of membrane proteins to the cytoskeleton in epithelial and specialized tissue including the heart. There is clear evidence to support the central role of intracellular auxiliary proteins in arrhythmogenesis and previous studies have found altered ZO-1 expression associated with atrioventricular conduction abnormalities. Here, using human cardiac tissues, we identified all three isoforms of ZO-1, canonical (Transcript Variant 1, TV1), CRA_e (Transcript Variant 4, TV4), and an additionally expressed (Transcript Variant 3, TV3) in non-failing myocardium. To investigate the role of ZO-1 on ventricular arrhythmogenesis, we generated a haploinsufficient ZO-1 mouse model (ZO-1+/−). ZO-1+/− mice exhibited dysregulated connexin-43 protein expression and localization at the intercalated disc. While ZO-1+/− mice did not display abnormal cardiac function at baseline, adrenergic challenge resulted in rhythm abnormalities, including premature ventricular contractions and bigeminy. At baseline, ventricular myocytes from the ZO-1+/− mice displayed prolonged action potential duration and spontaneous depolarizations, with ZO-1+/− cells displaying frequent unsolicited (non-paced) diastolic depolarizations leading to spontaneous activity with multiple early afterdepolarizations (EADs). Mechanistically, ZO-1 deficient myocytes displayed a reduction in sodium current density (INa) and an increased sensitivity to isoproterenol stimulation. Further, ZO-1 deficient myocytes displayed remodeling in ICa current, likely a compensatory change. Taken together, our data suggest that ZO-1 deficiency results in myocardial substrate susceptible to triggered arrhythmias.

To ensure accurate predictions of behavior and life-cycle of components in their real-use environment, it is essential to develop accurate simulation and testing procedures that reflect such an environment. For components on machines that experience a significant dynamic environment (such as airplanes, missiles, and automobiles), creating testing procedures that accurately mimic such a complex and harsh environment is a significant challenge. Often, testing a system by subjecting it to its operating environment is prohibitive due to cost and testing limitations. Thus, the usefulness of bench testing components through a testing procedure that mimics an operating environment is clear. Structural environmental testing is typically performed using a shaker to apply an environment to a component. However, shaker testing is currently limited in its ability to recreate environments because it often involves excitation in only one axis, when the system experiences a six degree of freedom excitation in practice. Additionally, there are many issues in matching boundary conditions in environmental testing.

OBJECTIVE Despite calls to increase prognosis communication for adolescents with cancer, limited research has examined their perceptions of prognosis as compared with their parents. We assessed adolescents' understanding of their prognosis relative to parents and oncologists. METHODS Families of adolescents (aged 10-17) were recruited at two pediatric institutions following a new diagnosis or relapse. Seventy-four adolescents, 68 mothers, and 40 fathers participated at enrollment; 76 adolescents, 69 mothers, and 35 fathers participated one year later. The adolescent's primary oncologist reported on prognosis only at enrollment. Participants rated the likelihood of the adolescent's survival in five years, as well as reporting prognosis communication and sources of information. RESULTS Most oncologists (65%) and fathers (63%) discussed prognosis in numerical terms with the adolescent at baseline, which was greater than mother report (49%) of discussions of numerical prognosis with adolescents. Adolescents reported a better prognosis than oncologists, but comparable with mothers at diagnosis and one year. Adolescents' prognosis estimates were stable over time (P > .05). At diagnosis, adolescent-father (P = 0.025) and adolescent-oncologist (P

Aortic compliance has been well established as an independent predictor of cardiovascular morbidity and mortality. The current "gold standard" for assessing aortic compliance is to use the carotid-femoral pulse-wave velocity (PWV) as a surrogate; however, PWV alone has been discussed in the literature as being inadequate for assessing compliance, especially for elderly patients and others who have a stiff aorta. In this paper an equation for the aortic compliance is developed using two approaches: 1) lumped-parameter modeling based on blood-pressure data and 2) distributed modeling based on the PWV. In-vitro experiments are conducted using a silicone-rubber tube which simulates the aorta, and an actual aorta harvested from a 1-year old, Holstein heifer. For both the rubber aorta and the Holstein aorta, a comparison is made between the blood-pressure model and the PWV model. In conclusion it is shown that good agreement exists between the two models, suggesting that either model may be used depending upon the available data. Furthermore, due to differences in material properties, it is shown that the compliance of the rubber aorta increases with mean arterial-pressure, while the compliance of the Holstein aorta decreases with mean arterial-pressure. Clinical implications of this research are also discussed.

In this paper, an efficiency map is created for a double-acting, single-rod hydraulic-actuator using a critically centered four-way spool valve and a load-sensing pump. The purpose of this research is to provide an understanding of the performance of a valve-controlled hydraulic actuator under all operating conditions. This paper considers a four-quadrant set of operating conditions, where each quadrant represents a different combination of actuator retraction or extension and overrunning or resistive loading. This four-quadrant efficiency map is the first presentation of its kind in the literature, and clearly demonstrates the performance characteristics and limitations for this hydraulic system. For its most common operation of an actuator extending under a resistive load, the map shows that this system can operate at over 82% efficiency and can move large loads. The map also shows physical limitations for the system, such as maximum pressure limits, maximum displacement limits, and valve limits. The efficiency map is plotted in nondimensional form, which presents the most general understanding of system performance and also allows dimensional values to be reconstructed for a similar system of any size.

Limb girdle muscular dystrophy type 2B (LGMD2B) and other dysferlinopathies are degenerative muscle diseases that result from mutations in the dysferlin gene and have limited treatment options. The dysferlin protein has been linked to multiple cellular functions including a Ca2+-dependent membrane repair process that reseals disruptions in the sarcolemmal membrane. Recombinant human MG53 protein (rhMG53) can increase the membrane repair process in multiple cell types both in vitro and in vivo. Here, we tested whether rhMG53 protein can improve membrane repair in a dysferlin-deficient mouse model of LGMD2B (B6.129-Dysftm1Kcam/J). We found that rhMG53 can increase the integrity of the sarcolemmal membrane of isolated muscle fibers and whole muscles in a Ca2+-independent fashion when assayed by a multi-photon laser wounding assay. Intraperitoneal injection of rhMG53 into mice before acute eccentric treadmill exercise can decrease the release of intracellular enzymes from skeletal muscle and decrease the entry of immunoglobulin G and Evans blue dye into muscle fibers in vivo. These results indicate that short-term rhMG53 treatment can ameliorate one of the underlying defects in dysferlin-deficient muscle by increasing sarcolemmal membrane integrity. We also provide evidence that rhMG53 protein increases membrane integrity independently of the canonical dysferlin-mediated, Ca2+-dependent pathway known to be important for sarcolemmal membrane repair.

The obscurin family of polypeptides is essential for normal striated muscle function and contributes to the pathogenesis of fatal diseases, including cardiomyopathies and cancers. The single mammalian obscurin gene, OBSCN, gives rise to giant (∼800 kDa) and smaller (∼40-500 kDa) proteins that are composed of tandem adhesion and signaling motifs. Mammalian obscurin proteins are expressed in a variety of cell types, including striated muscles, and localize to distinct subcellular compartments where they contribute to diverse cellular processes. Obscurin homologs in Caenorhabditis elegans and Drosophila possess a similar domain architecture and are also expressed in striated muscles. The long sought after question, "what does obscurin do?" is complex and cannot be addressed without taking into consideration the subcellular distribution of these proteins and local isoform concentration. Herein, we present an overview of the functions of obscurins and begin to define the intricate relationship between their subcellular distributions and functions in striated muscles.

The apparent volumetric displacement of digital displacement pumps and motors is reduced with increasing fluid pressure. So-called pump shrinkage has been documented in previous publications, where fluid compressibility effects were assumed to affect input and output power equally. In this paper, the authors derive the torque and flow rate of an ideal digital displacement pump. It is shown that the output power shrinks slightly more than the input. The difference between input and output shrinkage is counted as a power loss according to the accepted definition of total efficiency. New equations are presented for calculating mechanical and volumetric efficiencies which are up to 2% more accurate than the previous method (which assumes equal shrinkage) and up to 5% more accurate than conventional equations (which assume no shrinkage). Compressibility effects may be even more significant depending on pump design parameters, fluid properties, flow control algorithms and operating conditions. Calculations of partial pump efficiencies require a derived displacement volume to be known. The derived displacement volume of digital displacement pumps is considered for the first time in this paper. The contributions of this work are instructive for understanding the unique characteristics of digital displacement pumps as well as check-valve type pumps in general.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed for cardiac cell transplantation studies more than a decade ago. In order to establish the hiPSC-CM-based platform as an autologous source for cardiac repair and drug toxicity, it is vital to understand the functionality of cardiomyocytes. Therefore, the goal of this study was to assess functional physiology, ultrastructural morphology, gene expression, and microRNA (miRNA) profiling at Wk-1, Wk-2 & Wk-4 in hiPSC-CMs in vitro. Functional assessment of hiPSC-CMs was determined by multielectrode array (MEA), Ca2+ cycling and particle image velocimetry (PIV). Results demonstrated that Wk-4 cardiomyocytes showed enhanced synchronization and maturation as compared to Wk-1 & Wk-2. Furthermore, ultrastructural morphology of Wk-4 cardiomyocytes closely mimicked the non-failing (NF) adult human heart. Additionally, modulation of cardiac genes, cell cycle genes, and pluripotency markers were analyzed by real-time PCR and compared with NF human heart. Increasing expression of fatty acid oxidation enzymes at Wk-4 supported the switching to lipid metabolism. Differential regulation of 12 miRNAs was observed in Wk-1 vs Wk-4 cardiomyocytes. Overall, this study demonstrated that Wk-4 hiPSC-CMs showed improved functional, metabolic and ultrastructural maturation, which could play a crucial role in optimizing timing for cell transplantation studies and drug screening.

Preface. Introduction. I. FUNDAMENTALS. 1 Fluid Properties. 1.1 Introduction. 1.2 Fluid Mass Density. 1.3 Fluid Bulk Modulus. 1.4 Thermal Fluid Properties. 1.5 Fluid Viscosity. 1.6 Vapor Pressure. 1.7 Chemical Properties. 1.8 Fluid Types and Selection. 1.9 Conclusion. 1.10 References. 1.11 Homework Problems. 2 Fluid Mechanics. 2.1 Introduction. 2.2 Governing Equations. 2.3 Fluid Flow. 2.4 Pressure Losses. 2.5 Pressure Transients. 2.6 Hydraulic Energy and Power. 2.7 Lubrication Theory. 2.8 Conclusion. 2.9 References. 2.10 Homework Problems. 3 Dynamic Systems and Controls. 3.1 Introduction. 3.2 Modeling. 3.3 Linearization. 3.4 Dynamic Behavior. 3.5 State-Space Analysis. 3.6 Block Diagrams and the Laplace Transform. 3.7 Stability. 3.8 Compensation. 3.9 Conclusion. 3.10 References. 3.11 Homework Problems. II HYDRAULIC COMPONENTS. 4 Hydraulic Control Valves. 4.1 Introduction. 4.2 Valve Flow Coefficients. 4.3 Two-Way Spool Valves. 4.4 Three-Way Spool Valves. 4.5 Four-Way Spool Valves. 4.6 Poppet Valves. 4.7 Flapper Nozzle Valves. 4.8 Conclusion. 4.9 References. 4.10 Homework Problems. 5 Hydraulic Pumps. 5.1 Introduction. 5.2 Pump Efficiency. 5.3 Gear Pumps. 5.4 Axial-Piston Swash-Plate Pumps. 5.5 Conclusion. 5.6 References. 5.7 Homework Problems. 6 Hydraulic Actuators. 6.1 Introduction. 6.2 Actuator Types. 6.3 Linear Actuators. 6.4 Rotary Actuators. 6.5 Conclusion. 6.6 References. 6.7 Homework Problems. III HYDRAULIC CONTROL SYSTEMS. 7 Valve-Controlled Hydraulic Systems. 7.1 Introduction. 7.2 Four-Way Valve Control of a Linear Actuator. 7.3 Three-Way Valve Control of a Linear Actuator. 7.4 Four-Way Valve Control of a Rotary Actuator. 7.5 Conclusion. 7.6 References. 7.7 Homework Problems. 8 Pump-Controlled Hydraulic Systems. 8.1 Introduction. 8.2 Fixed-Displacement Pump Control of a Linear Actuator. 8.3 Variable-Displacement Pump Control of a Rotary Actuator. 8.4 Conclusion. 8.5 References. 8.6 Homework Problems. INDEX.

Using a unique inlet metering pump with fixed displacement and speed, this work introduces a new way to control a linear hydraulic actuator velocity. The inlet metering system consists of an inlet metering valve that adjusts the hydraulic fluid flow that enters the pump and a fixed displacement pump. Fluid is supplied to the inlet metering valve at a fixed pressure. Energy losses associated with flow metering in the system are reduced because the pressure drop across the inlet metering valve can be small compared to a traditional valve-controlled system. A velocity control system is designed using the inlet metering pump to control the fluid flow into a hydraulic cylinder. First, the valve dynamic model is ignored, the open-loop response is studied, and closed-loop proportional and proportional derivative controllers are designed. Next, the valve dynamic model is included and closed-loop proportional integral derivative, H∞, and two-degrees-of-freedom controllers are designed. Designs with the goals of stability and performance of the system are considered so that a precise velocity control system for the hydraulic cylinder is achieved. In addition to the potentially high efficiency of this system, there is potential for low-cost, fast-response, and less complicated dynamics compared to other systems. The results show that the velocity control system can be designed so that the system is stable for all cases and with 0% overshoot and no oscillation depending on valve dynamics using the two-degrees-of-freedom controller for tracking the desired velocity.