A Data-Driven Computational Model for Engineered Cardiac Microtissues

Engineered heart tissues (EHTs) present a potential solution to some of the current challenges in the treatment of heart disease; however, the development of mature, adult-like cardiac tissues remains elusive. Mechanical stimuli have been observed to improve whole-tissue function and cardiomyocyte (CM) maturation, although our ability to fully utilize these mechanisms is hampered, in part, by our incomplete understanding of the mechanobiology of EHTs. In this work, we leverage the experimental data produced by a mechanically tunable experimental setup to generate tissue-specific computational models of EHTs. Using imaging and functional data, our modeling pipeline generates models with tissue-specific ECM and myofibril structure, allowing us to estimate CM active stress. We use this experimental and modeling pipeline to study different mechanical environments, where we contrast the force output of the tissue with the computed active stress of CMs. We show that the significant differences in measured experimental forces can largely be explained by the levels of myofibril formation achieved by the CMs in the distinct mechanical environments, with active stress showing more muted variations across conditions. The presented model also enables us to dissect the relative contributions of myofibrils and extracellular matrix to tissue force output, a task difficult to address experimentally. These results highlight the importance of tissue-specific modeling to augment EHT experiments, providing deeper insights into the mechanobiology driving EHT function.Comment: 19 pages, 7 figure

Identification and quantification of particle growth channels during new particle formation

Atmospheric new particle formation (NPF) is a key source of ambient ultrafine particles that may contribute substantially to the global production of cloud condensation nuclei (CCN). While NPF is driven by atmospheric nucleation, its impact on CCN concentration depends strongly on atmospheric growth mechanisms since the growth rate must exceed the loss rate due to scavenging in order for the particles to reach the CCN size range. In this work, chemical composition measurements of 20 nm diameter particles during NPF in Hyytiälä, Finland, in March–April 2011 permit identification and quantitative assessment of important growth channels. In this work we show the following: (A) sulfuric acid, a key species associated with atmospheric nucleation, accounts for less than half of particle mass growth during this time period; (B) the sulfate content of a growing particle during NPF is quantitatively explained by condensation of gas-phase sulfuric acid molecules (i.e., sulfuric acid uptake is collision-limited); (C) sulfuric acid condensation substantially impacts the chemical composition of preexisting nanoparticles before new particles have grown to a size sufficient to be measured; (D) ammonium and sulfate concentrations are highly correlated, indicating that ammonia uptake is driven by sulfuric acid uptake; (E) sulfate neutralization by ammonium does not reach the predicted thermodynamic end point, suggesting that a barrier exists for ammonia uptake; (F) carbonaceous matter accounts for more than half of the particle mass growth, and its oxygen-to-carbon ratio (~ 0.5) is characteristic of freshly formed secondary organic aerosol; and (G) differences in the overall growth rate from one formation event to another are caused by variations in the growth rates of all major chemical species, not just one individual species

National Athletic Trainers\u27 Association Position Statement: Safe Weight Loss and Maintenance Practices in Sport and Exercise

Objective: To present athletic trainers with recommendations for safe weight loss and weight maintenance practices for athletes and active clients and to provide athletes, clients, coaches, and parents with safe guidelines that will allow athletes and clients to achieve and maintain weight and body composition goals. Background: Unsafe weight management practices can compromise athletic performance and negatively affect health. Athletes and clients often attempt to lose weight by not eating, limiting caloric or specific nutrients from the diet, engaging in pathogenic weight control behaviors, and restricting fluids. These people often respond to pressures of the sport or activity, coaches, peers, or parents by adopting negative body images and unsafe practices to maintain an ideal body composition for the activity. We provide athletic trainers with recommendations for safe weight loss and weight maintenance in sport and exercise. Although safe weight gain is also a concern for athletic trainers and their athletes and clients, that topic is outside the scope of this position statement. Recommendations: Athletic trainers are often the source of nutrition information for athletes and clients; therefore, they practices, and methods to change body composition. Body composition assessments should be done in the most scientifically appropriate manner possible. Reasonable and individualized weight and body composition goals should be identified by appropriately trained health care personnel (eg, athletic trainers, registered dietitians, physicians). In keeping with the American Dietetics Association (ADA) preferred nomenclature, this document uses the terms registered dietitian or dietician when referring to a food and nutrition expert who has met the academic and professional requirements specified by the ADA\u27s Commission on Accreditation for Dietetics Education. In some cases, a registered nutritionist may have equivalent credentials and be the commonly used term. All weight management and exercise protocols used to achieve these goals should be safe and based on the most current evidence. Athletes, clients, parents, and coaches should be educated on how to determine safe weight and body composition so that athletes and clients more safely achieve competitive weights that will meet sport and activity requirements while also allowing them to meet their energy and nutritional needs for optimal health and performance

Advanced Electrocardiographic Predictors of Sudden Death in Familial Dysautonomia

To identify accurate predictors for the risk of sudden death in patients with familial dysautonomia (FD). Ten-minute resting high-fidelity 12-lead ECGs were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict sudden death in FD over a subsequent 4.5-year period, including multiple indices of linear and non-linear heart rate variability (HRV); QT variability; waveform complexity; high frequency QRS; and derived Frank-lead parameters. Four of the 14 FD patients died suddenly during the follow-up period, usually with concomitant pulmonary disorder. The presence of low vagally-mediated HRV was the ECG finding most predictive of sudden death. Concomitant left ventricular hypertrophy and other ECG abnormalities such as increased QTc and JTc intervals, spatial QRS-T angles, T-wave complexity, and QT variability were also present in FD patients, suggesting that structural heart disease is fairly common in FD. Although excessive or unopposed cardiac vagal (relative to sympathetic) activity has been postulated as a contributor to sudden death in FD, the presence of low vagally-mediated HRV was paradoxically the best predictor of sudden death. However, we suggest that low vagally-mediated HRV be construed not as a direct cause of sudden death in FD, but rather as an effect of concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea, that themselves increase the risk of sudden death in FD and simultaneously diminish HRV. We speculate that adenosine may play a role in sudden death in FD, possibly independently of vagal activity, and that adenosine inhibitors such as theophylline might therefore be useful as prophylaxis in this disorder

Detecting and Characterizing Young Quasars. III. the Impact of Gravitational Lensing Magnification

We test the impact of gravitational lensing on the lifetime estimates of seven high-redshift quasars at redshift z 3 6. The targeted quasars are identified by their small observed proximity zone sizes, which indicate extremely short quasar lifetimes (t Q 2 105yr). However, these estimates of quasar lifetimes rely on the assumption that the observed luminosities of the quasars are intrinsic and not magnified by gravitational lensing, which would bias the lifetime estimates toward younger ages. In order to test the possible effects of gravitational lensing, we obtain high-resolution images of the seven quasars with the Hubble Space Telescope and look for signs of strong lensing. We do not find any evidence of strong lensing, i.e., all quasars are well described by point sources, and no foreground lensing galaxy is detected. We estimate that the strong-lensing probabilities for these quasars are extremely small ( 1/41.4 × 10-5) and show that weak lensing changes the estimated quasar lifetimes by only 20.2 dex. We thus confirm that the short lifetimes of these quasars are intrinsic. The existence of young quasars indicates a high obscured fraction, radiatively inefficient accretion, and/or flickering lightcurves for high-redshift quasars. We further discuss the impact of lensing magnification on measurements of black hole masses and Eddington ratios of quasars

MicroBundleCompute: Automated segmentation, tracking, and analysis of subdomain deformation in cardiac microbundles

Advancing human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) technology will lead to significant progress ranging from disease modeling, to drug discovery, to regenerative tissue engineering. Yet, alongside these potential opportunities comes a critical challenge: attaining mature hiPSC-CM tissues. At present, there are multiple techniques to promote maturity of hiPSC-CMs including physical platforms and cell culture protocols. However, when it comes to making quantitative comparisons of functional behavior, there are limited options for reliably and reproducibly computing functional metrics that are suitable for direct cross-system comparison. In addition, the current standard functional metrics obtained from time-lapse images of cardiac microbundle contraction reported in the field (i.e., post forces, average tissue stress) do not take full advantage of the available information present in these data (i.e., full-field tissue displacements and strains). Thus, we present "MicroBundleCompute," a computational framework for automatic quantification of morphology-based mechanical metrics from movies of cardiac microbundles. Briefly, this computational framework offers tools for automatic tissue segmentation, tracking, and analysis of brightfield and phase contrast movies of beating cardiac microbundles. It is straightforward to implement, requires little to no parameter tuning, and runs quickly on a personal computer. In this paper, we describe the methods underlying this computational framework, show the results of our extensive validation studies, and demonstrate the utility of exploring heterogeneous tissue deformations and strains as functional metrics. With this manuscript, we disseminate "MicroBundleCompute" as an open-source computational tool with the aim of making automated quantitative analysis of beating cardiac microbundles more accessible to the community.Comment: 16 main pages, 7 main figures, Supplementary Information included as appendice

Seasonal calibration of the end-cretaceous Chicxulub impact event

The end-Cretaceous Chicxulub impact triggered Earth’s last mass-extinction, extinguishing ~ 75% of species diversity and facilitating a global ecological shift to mammal-dominated biomes. Temporal details of the impact event on a fine scale (hour-to-day), important to understanding the early trajectory of mass-extinction, have largely eluded previous studies. This study employs histological and histo-isotopic analyses of fossil fish that were coeval with a unique impact-triggered mass-death assemblage from the Cretaceous-Paleogene (KPg) boundary in North Dakota (USA). Patterns of growth history, including periodicity of ẟ18O and ẟ13C and growth band morphology, plus corroborating data from fish ontogeny and seasonal insect behavior, reveal that the impact occurred during boreal Spring/Summer, shortly after the spawning season for fish and most continental taxa. The severity and taxonomic symmetry of response to global natural hazards are influenced by the season during which they occur, suggesting that post-impact perturbations could have exerted a selective force that was exacerbated by seasonal timing. Data from this study can also provide vital hindsight into patterns of extant biotic response to global-scale hazards that are relevant to both current and future biomes

Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile

In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also

\u201cGive, but Give until It Hurts\u201d: The Modulatory Role of Trait Emotional Intelligence on the Motivation to Help

Two studies investigated the effect of trait Emotional Intelligence (trait EI) on people\u2019s moti- vation to help. In Study 1, we developed a new computer-based paradigm that tested partic- ipants\u2019 motivation to help by measuring their performance on a task in which they could gain a hypothetical amount of money to help children in need. Crucially, we manipulated partici- pants\u2019 perceived efficacy by informing them that they had been either able to save the chil- dren (positive feedback) or unable to save the children (negative feedback). We measured trait EI using the Trait Emotional Intelligence Questionnaire\u2013Short Form (TEIQue-SF) and assessed participants\u2019 affective reactions during the experiment using the PANAS-X. Results showed that high and low trait EI participants performed differently after the presen- tation of feedback on their ineffectiveness in helping others in need. Both groups showed increasing negative affective states during the experiment when the feedback was negative; however, high trait EI participants better managed their affective reactions, modulating the impact of their emotions on performance and maintaining a high level of motivation to help. In Study 2, we used a similar computerized task and tested a control situation to explore the effect of trait EI on participants\u2019 behavior when facing failure or success in a scenario unre- lated to helping others in need. No effect of feedback emerged on participants\u2019 emotional states in the second study. Taken together our results show that trait EI influences the impact of success and failure on behavior only in affect-rich situation like those in which people are asked to help others in need