What is the Relative Timing Between Myosin’s Powerstroke and Pi-release?

Myosins are a family of motor proteins responsible for various forms of cellular motility, including muscle contraction and vesicular transport. The most fundamental aspect of myosin is its ability to transduce the chemical energy from the hydrolysis of ATP into mechanical work, in the form of force and motion. A key unanswered question of the transduction process is, ”what is the relative timing between the pow- erstroke and release of phosphate Pi from the active site?”. We examined the ability of single-headed myosin Va to generate a powerstroke in a single molecule laser trap assay while maintaining Pi in its active site in of of two ways: 1) by elevating Pi in solution or 2) by introducing a mutation in myosin’s active site (S217A) which slow Pi-release from the active site. An autaomted analysis program for the detection of single molecule binding events was developed and showed that upon binding to the actin filament, WT myosin generated a powerstoke rapidly (500/s) and without a detectable delay, both in the absence and presence of 30 mM Pi . The elevated levels of Pi did, however, affect event lifetime, eliminating the longest 25 percent of binding events, confirming that Pi rebound to myosin’s active site and accelerated detachment. The S217A construct also generated a powerstroke similar in size and rate upon binding to actin despite the slower Pi release rate. These findings provide direct evidence that myosin Va generates a powerstroke with Pi still in the active site. Therefore, the findings are most consistent with a model in which the powerstroke occurs prior to the release of Pi from the active site

Tropomyosin-Based Effects of Acidosis on Thin-Filament Regulation During Muscle Fatigue

Skeletal muscle fatigue is defined as a loss in the force/velocity generating capacity of a muscle. A portion of the loss in function is attributable to effects of acidosis (i.e. low pH) on the regulatory proteins, troponin and tropomyosin (Tm), which regulate the binding of myosin and actin in a calcium (Ca++) dependent manner. However, the relative role of troponin and Tm on myosin-actin function during acidosis is not clear, nor are the mechanisms underlying these effects. PURPOSE: To determine the role of Tm in the acidosis-induced depression of muscle function using isolated muscle proteins in an in vitro motility assay. METHODS: Three mutant constructs of Tm were expressed by replacing the two amino acid (histidine) residues most likely affected by low pH with alanine residues (H153A, H276A, H153A/H276A). These mutant constructs were compared to wild-type Tm (wt-Tm) in order to test whether the acidosis-induced charge change of the histidine amino acid governs the pH-dependent alteration of tropomyosin and therefore the decrease in maximal RTF velocity and Ca++-sensitivity. The effect of acidosis on regulated thin filament (RTF) function was determined by assessing the impact of low pH (pH 6.8) versus neutral pH (pH 7.4) on myosin’s ability to move RTFs in the motility assay as a function of increasing levels of Ca++. This was done separately for the wt-Tm and each structural variant. RESULTS: A two-way ANOVA (pH x Tm construct) revealed that acidosis significantly (p\u3c0.05) depressed the maximal sliding velocity of the RTFs across all versions of Tm, but that the magnitude of the depression was similar among the wt and all of the Tm mutants. Acidosis did not significantly depress the sensitivity to Ca++ under the unloaded conditions of this assay (p\u3e0.05). CONCLUSIONS: These data suggest that the histidine residues in tropomyosin do not mediate the acidosis-induced depression in contraction velocity observed during muscle fatigue. However, since these residues may be more important in mediating the depression of force, we are currently testing the impact of the three mutant Tm constructs on the acidosis-induced depression in Ca++-sensitivity using a loaded in vitro motility assay

A critical edition of John Pickering's Horestes

Thesis (M.A.)--Boston University, 1947The play under discussion has been classed by Tucker Brooke as a moral interlude which developed from the Morality Play of the fifteenth and sixteenth centuries. Although comic interludes were popular in the middle of the sixteenth century, tragedies and historical plays had also begun to make their appearance, and the Horestes was the first historical play with a classical source to appear on the English Stage. It was also the first play in England to use the revenge of a father theme which Kyd and Shakespeare used so successfully at the turn of the century. Other historical plays like Bishop Bayle's King John and Sackville and Norton's Gorboduc chose rather to us the native history of England as a basis for their drama

Appropriability and Commercialization: Evidence from MIT Inventions

At least since Arrow (1962), the effects of appropriability on invention have been well studied, but there has been little analysis of the effect of appropriability on the commercialization of existing inventions. Exploiting a database of 805 attempts by private firms to commercialize inventions licensed from MIT between 1980 and 1996, we explore the influence of several appropriability mechanisms on the commercialization and termination of projects to develop products based on university inventions. We construct a theoretical model in which the licensee faces technical and market uncertainty, and anticipates that its products will be imitated. We characterize the hazards of commercialization and termination as functions of appropriability mechanisms, including patent scope and the effectiveness of patents as well as learning, lead time, and secrecy in attaining competitive advantage. The model is tested using a competing risks framework that allows for non-parametric unobserved heterogeneity and correlated risks. In our sample, patent strength and secrecy influence termination decisions, while learning, patent scope and lead time influence commercialization decisions.hazard rates, innovation, optimal stopping problem, patent scope, university licensing, termination

Unsupervised Time Series Extraction from Controller Area Network Payloads

This paper introduces a method for unsupervised tokenization of Controller Area Network (CAN) data payloads using bit level transition analysis and a greedy grouping strategy. The primary goal of this proposal is to extract individual time series which have been concatenated together before transmission onto a vehicle's CAN bus. This process is necessary because the documentation for how to properly extract data from a network may not always be available; passenger vehicle CAN configurations are protected as trade secrets. At least one major manufacturer has also been found to deliberately misconfigure their documented extraction methods. Thus, this proposal serves as a critical enabler for robust third-party security auditing and intrusion detection systems which do not rely on manufacturers sharing confidential information.Comment: 2018 IEEE 88th Vehicular Technology Conference (VTC2018-Fall

Uncertainty and Producer Fed Cattle Marketing Decisions: Theory and Evidence

The effect of carcass quality uncertainty on the structure of the slaughter cattle market is investigated. A theoretical extension of the “Theory of Factor Price Disparity” is provided. It is demonstrated that the coexistence of a risk premium wedge between pricing mechanisms (live wt., dressed wt., and grid) in conjunction with varying degrees of risk aversion across fed cattle producers explains the coexistence of multiple pricing mechanisms. It is also demonstrated that risk and risk preference provides a plausible explanation for the structure of the fed cattle market and for the variability in slaughter volume across marketing channels. Empirical evidence is provided in support of the supposition that carcass quality uncertainty plays a role in grid market share variability

Junior Recital: Madeline Scott, soprano

This recital is presented in partial fulfillment of requirements for the degree Bachelor of Music in Performance. Ms. Scott studies voice with Oral Moses.https://digitalcommons.kennesaw.edu/musicprograms/1438/thumbnail.jp

Appropriability and the timing of innovation: Evidence from MIT inventions

At least since Arrow (1962), the effects of appropriability on invention have been well studied, but there has been little analysis of the effect of appropriability on the commercialization of existing inventions. Exploiting a database of 805 attempts by private firms to commercialize inventions licensed from MIT between 1980 and 1996, we explore the influence of several appropriability mechanisms on the commercialization and termination of projects to develop products based on university inventions. Our central hypothesis is that the relationship between a licensee's decision to either terminate or commercialize the invention is driven by the current market value of the invention, as well as the option value of delaying its commercialization. We use a competing risks framework that allows for non- parametric heterogeneity and correlated risks. We find that better appropriability in the sense of more effective patent strength and secrecy has a strong negative effect on the hazard of license termination. The effectiveness of learning has a strong positive effect on the hazard of technology commercialization, while lead time has a negative effect.