Sub-nanomolar detection of thrombin activity on a microfluidic chip

Bioluminescence resonance energy transfer (BRET) is a form of Förster resonance energy transfer. BRET has been shown to support lower limits of detection than fluorescence resonance energy transfer (FRET) but, unlike FRET, has not been widely implemented on microfluidic devices for bioanalytical sensing. We recently reported a microscope-based microfluidic system for BRET-based biosensing, using a hybrid, high quantum-efficiency, form of BRET chemistry. This paper reports the first optical fiber-based system for BRET detection on a microfluidic chip, capable of quantifying photon emissions from the low quantum-efficiency BRET² system. We investigated the effects of varying core diameter and numerical aperture of optical fibers, as well as varying microfluidic channel design and measurement conditions. We optimized the set-up in order to maximize photon counts and minimize the response time. The optimized conditions supported measurement of thrombin activity, with a limit of detection of 20 pM, which is lower than the microscope-based system and more than 20 times lower than concentrations reported to occur in plasma clots.     

Musculoskeletal stiffness during hopping and running does not change following downhill backwards walking

Eccentric contractions that provide spring energy can also cause muscle damage. The aim of this study was to explore leg and vertical stiffness following muscle damage induced by an eccentric exercise protocol. Twenty active males completed 60 minutes of backward-walking on a treadmill at 0.67 m/s and a gradient of ? 8.5° to induce muscle damage. Tests were performed immediately before; immediately post; and 24, 48, and 168 hours post eccentric exercise. Tests included running at 3.35 m/s and hopping at 2.2 Hz using single- and double-legged actions. Leg and vertical stiffness were measured from kinetic and kinematic data, and electromyography (EMG) of five muscles of the preferred limb were recorded during hopping. Increases in pain scores (over 37%) occurred post-exercise and 24 and 48 hours later (p < 0.001). A 7% decrease in maximal voluntary contraction occurred immediately post-exercise (p = 0.019). Changes in knee kinematics during single-legged hopping were observed 168 hours post (p < 0.05). No significant changes were observed in EMG, creatine kinase activity, leg, or vertical stiffness. Results indicate that knee mechanics may be altered to maintain consistent levels of leg and vertical stiffness when eccentric exercise-induced muscle damage is present in the lower legs.     

Embellishing Problem-Solving Examples with Deep Structure Information Facilitates Transfer

Appreciation of problem structure is critical to successful learning. Two experiments investigated effective ways of communicating problem structure in a computer-based learning environment and tested whether verbal instruction is necessary to specify solution steps, when deep structure is already embellished by instructional examples. Participants learned to solve algebra-like problems and then solved transfer problems that required adjustment of learned procedures. Experiment 1 demonstrated that verbal instruction helped learning by reducing learners' floundering, but its positive effect disappeared in the transfer. More importantly, students transferred better when they studied with examples that emphasized problem structure rather than solution procedure. Experiment 2 showed that verbal instruction was not necessarily more effective than nonverbal scaffolding to convey problem structure. Final understanding was determined by transparency of problem structure regardless of presence of verbal instruction. However, verbal instruction had a positive impact on learners by having them persist through the task, and optimal instructional choices were likely to differ depending on populations of learners.     

A Criterion-Referenced Approach to Student Ratings of Instruction

We developed a criterion-referenced student rating of instruction (SRI) to facilitate formative assessment of teaching. It involves four dimensions of teaching quality that are grounded in current instructional design principles: Organization and structure, Assessment and feedback, Personal interactions, and Academic rigor. Using item response theory and Wright mapping methods, we describe teaching characteristics at various points along the latent continuum for each scale. These maps enable criterion-referenced score interpretation by making an explicit connection between test performance and the theoretical framework. We explain the way our Wright maps can be used to enhance an instructor’s ability to interpret scores and identify ways to refine teaching. Although our work is aimed at improving score interpretation, a criterion-referenced test is not immune to factors that may bias test scores. The literature on SRIs is filled with research on factors unrelated to teaching that may bias scores. Therefore, we also used multilevel models to evaluate the extent to which student and course characteristic may affect scores and compromise score interpretation. Results indicated that student anger and the interaction between student gender and instructor gender are significant effects that account for a small amount of variance in SRI scores. All things considered, our criterion-referenced approach to SRIs is a viable way to describe teaching quality and help instructors refine pedagogy and facilitate course development.     

Impaired acuity of the approximate number system underlies mathematical learning disability (dyscalculia)

Many children have significant mathematical learning disabilities (MLD, or dyscalculia) despite adequate schooling. The current study hypothesizes that MLD partly results from a deficiency in the Approximate Number System (ANS) that supports nonverbal numerical representations across species and throughout development. In this study of 71 ninth graders, it is shown that students with MLD have significantly poorer ANS precision than students in all other mathematics achievement groups (low, typically, and high achieving), as measured by psychophysical assessments of ANS acuity (w) and of the mappings between ANS representations and number words (cv). This relation persists even when controlling for domain-general abilities. Furthermore, this ANS precision does not differentiate low-achieving from typically achieving students, suggesting an ANS deficit that is specific to MLD.     

Novel model reference adaptive control laws for improved transient dynamics and guaranteed saturation constraints

In classical model reference adaptive control (MRAC), the adaptive rates must be tuned to meet multiple competing objectives. Large adaptive rates guarantee rapid convergence of the trajectory tracking error to zero. However, large adaptive rates may also induce saturation of the actuators and excessive overshoots of the closed-loop system’s trajectory tracking error. Conversely, low adaptive rates may produce unsatisfactory trajectory tracking performances. To overcome these limitations, in the classical MRAC framework, the adaptive rates must be tuned through an iterative process. Alternative approaches require to modify the plant’s reference model or the reference command input. This paper presents the first MRAC laws for nonlinear dynamical systems affected by matched and parametric uncertainties that constrain both the closed-loop system’s trajectory tracking error and the control input at all times within user-defined bounds, and enforce a user-defined rate of convergence on the trajectory tracking error. By applying the proposed MRAC laws, the adaptive rates can be set arbitrarily large and both the plant’s reference model and the reference command input can be chosen arbitrarily. The user-defined rate of convergence of the closed-loop plant’s trajectory is enforced by introducing a user-defined auxiliary reference model, which converges to the trajectory tracking error obtained by applying the classical MRAC laws before its transient dynamics has decayed, and steering the trajectory tracking error to the auxiliary reference model at a rate of convergence that is higher than the rate of convergence of the plant’s reference model. The ability of the proposed MRAC laws to prescribe the performance of the closed-loop system’s trajectory tracking error and control input is guaranteed by barrier Lyapunov functions. Numerical simulations illustrate both the applicability of our theoretical results and their effectiveness compared to other techniques such as prescribed performance control, which allows to constrain both the rate of convergence and the maximum overshoot on the trajectory tracking error of uncertain systems.