UNDERSTANDING TECHNOLOGY ADOPTION THROUGH SYSTEM DYNAMICS MODELING: IMPLICATIONS FOR AGRIBUSINESS MANAGEMENT

This work demonstrates the utility of sophisticated simulation tools in aiding agribusiness managers' decision making. The system dynamics model developed here provides insight into the use of such models to evaluate potential adoption rates and diffusion patterns of yield mapping and monitoring technologies. The model allows for comparative analyses of the possible effects of different profit assumptions on adoption and diffusion.Agribusiness, Research and Development/Tech Change/Emerging Technologies,

Probing the Kinetic Stabilities of Friedreich’s Ataxia Clinical Variants Using a Solid Phase GroEL Chaperonin Capture Platform

Numerous human diseases are caused by protein folding defects where the protein may become more susceptible to degradation or aggregation. Aberrant protein folding can affect the kinetic stability of the proteins even if these proteins appear to be soluble in vivo. Experimental discrimination between functional properly folded and misfolded nonfunctional conformers is not always straightforward at near physiological conditions. The differences in the kinetic behavior of two initially folded frataxin clinical variants were examined using a high affinity chaperonin kinetic trap approach at 25 °C. The kinetically stable wild type frataxin (FXN) shows no visible partitioning onto the chaperonin. In contrast, the clinical variants FXN-p.Asp122Tyr and FXN-p.Ile154Phe kinetically populate partial folded forms that tightly bind the GroEL chaperonin platform. The initially soluble FXN-p.Ile154Phe variant partitions onto GroEL more rapidly and is more kinetically liable. These differences in kinetic stability were confirmed using differential scanning fluorimetry. The kinetic and aggregation stability differences of these variants may lead to the distinct functional impairments described in Friedreich’s ataxia, the neurodegenerative disease associated to frataxin functional deficiency. This chaperonin platform approach may be useful for identifying small molecule stabilizers since stabilizing ligands to frataxin variants should lead to a concomitant decrease in chaperonin binding

The connection between polymer collapse and the onset of jamming

Previous studies have shown that the interiors of proteins are densely packed, reaching packing fractions that are as large as those found for static packings of individual amino-acid-shaped particles. How can the interiors of proteins take on such high packing fractions given that amino acids are connected by peptide bonds and many amino acids are hydrophobic with attractive interactions? We investigate this question by comparing the structural and mechanical properties of collapsed attractive disk-shaped bead-spring polymers to those of three reference systems: static packings of repulsive disks, of attractive disks, and of repulsive disk-shaped bead-spring polymers. We show that attractive systems quenched to temperatures below the glass transition $T \ll T_g$ and static packings of both repulsive disks and bead-spring polymers possess similar interior packing fractions. Previous studies have shown that static packings of repulsive disks are isostatic at jamming onset, i.e. the number of contacts $N_c$ matches the number of degrees of freedom, which strongly influences their mechanical properties. We find that repulsive polymers are hypostatic at jamming onset, but effectively isostatic when including quartic modes. While attractive disk and polymer packings are hyperstatic, we identify a definition for interparticle contacts for which they can also be considered as effectively isostatic. As a result, we show that the mechanical properties (e.g. scaling of the potential energy with excess contact number and low-frequency contribution to the density of vibrational modes) of weakly attractive disk and polymer packings are similar to those of ${\it isostatic}$ repulsive disk and polymer packings. Our results demonstrate that static packings generated via attractive collapse or compression of repulsive particles possess similar structural and mechanical properties.Comment: 17 pages, 16 figures, 2 appendice

Analysis of Turbofan Design Options for an Advanced Single-Aisle Transport Aircraft

The desire for higher engine efficiency has resulted in the evolution of aircraft gas turbine engines from turbojets, to low bypass ratio, first generation turbofans, to today's high bypass ratio turbofans. It is possible that future designs will continue this trend, leading to very-high or ultra-high bypass ratio (UHB) engines. Although increased bypass ratio has clear benefits in terms of propulsion system metrics such as specific fuel consumption, these benefits may not translate into aircraft system level benefits due to integration penalties. In this study, the design trade space for advanced turbofan engines applied to a single-aisle transport (737/A320 class aircraft) is explored. The benefits of increased bypass ratio and associated enabling technologies such as geared fan drive are found to depend on the primary metrics of interest. For example, bypass ratios at which fuel consumption is minimized may not require geared fan technology. However, geared fan drive does enable higher bypass ratio designs which result in lower noise. Regardless of the engine architecture chosen, the results of this study indicate the potential for the advanced aircraft to realize substantial improvements in fuel efficiency, emissions, and noise compared to the current vehicles in this size class

Femtosecond Thermionic Emission in the Space-Charge Limited Regime

We study femtosecond-laser-pulse-induced electron emission from W(100), Al(110), and Ag(lll) in the sub-damage regime (1–44 mJ/cm2 fluence) by simultaneously measuring the incident-light reflectivity, total electron yield, and electron-energy distribution curves of the emitted electrons. The total-yield results are compared with a space-charge-limited extension of the Richardson-Dushman equation for short-time-scale thermionic emission and with particle-in-a-cell computer simulations of femtosecond-pulsed-induced thermionic emission. Quantitative agreement between the experimental results and two calculated temperature-dependent yields is obtained and shows that the yield varies linearly with temperature beginning at a threshold electron temperature of ~0.25 eV The particle-in-a-cell simulations also reproduce the experimental electron-energy distribution curves. Taken together, the experimental results, the theoretical calculations, and the results of the simulations indicate that thermionic emission from nonequilibrium electron heating provides the dominant source of the emitted electrons. Furthermore, the results demonstrate that a quantitative theory of space-charge-limited femtosecond-pulse-induced electron emission is possible

The development and evaluation of mini-GEMs: a short, focused, online e-learning videos in geriatric medicine

Mini Geriatric E-Learning Modules (Mini-GEMs) are short, focused, e-learning videos on geriatric medicine topics, hosted on YouTube, which are targeted at junior doctors working with older people. This study aimed to explore how these resources are accessed and used. The authors analyzed the viewing data from 22 videos published over the first 18 months of the Mini-GEM project. We conducted a focus group of U.K. junior doctors considering their experiences with Mini-GEMS. The Mini-GEMs were viewed 10,291 times over 18 months, equating to 38,435 minutes of total viewing time. The average viewing time for each video was 3.85 minutes. Learners valued the brevity and focused nature of the Mini-GEMs and reported that they watched them in a variety of settings to supplement clinical experiences and consolidate learning. Watching the videos led to an increase in self-reported confidence in managing older patients. Mini-GEMs can effectively disseminate clinical teaching material to a wide audience. The videos are valued by junior doctors due to their accessibility and ease of use

Refined Exploration of Turbofan Design Options for an Advanced Single-Aisle Transport

A comprehensive exploration of the turbofan engine design space for an advanced technology single-aisle transport (737/A320 class aircraft) was conducted previously by the authors and is documented in a prior report. Through the course of that study and in a subsequent evaluation of the approach and results, a number of enhancements to the engine design ground rules and assumptions were identified. A follow-on effort was initiated to investigate the impacts of these changes on the original study results. The fundamental conclusions of the prior study were found to still be valid with the revised engine designs. The most significant impact of the design changes was a reduction in the aircraft weight and block fuel penalties incurred with low fan pressure ratio, ultra-high bypass ratio designs. This enables lower noise levels to be pursued (through lower fan pressure ratio) with minor negative impacts on aircraft weight and fuel efficiency. Regardless of the engine design selected, the results of this study indicate the potential for the advanced aircraft to realize substantial improvements in fuel efficiency, emissions, and noise compared to the current vehicles in this size class

Urocortin 2 Infusion in Healthy Humans Hemodynamic, Neurohormonal, and Renal Responses

ObjectivesWe sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans.BackgroundUrocortin 2 is a vasoactive and cardioprotective peptide belonging to the corticotrophin-releasing factor peptide family. Recent reports indicate the urocortins exert important effects beyond the hypothalamo-pituitary-adrenal axis upon cardiovascular and vasohumoral function in health and cardiac disease.MethodsWe studied 8 healthy unmedicated men on 3 separate occasions 2 to 5 weeks apart. Subjects received placebo, 25-μg low-dose (LD), and 100-μg high-dose (HD) of UCN 2 intravenously over the course of 1 h in a single-blind, placebo-controlled, dose-escalation design. Noninvasive hemodynamic indexes, neurohormones, and renal function were measured.ResultsThe administration of UCN 2 dose-dependently increased cardiac output (mean peak increments ± SEM) (placebo 0.5 ± 0.2 l/min; LD 2.1 ± 0.6 l/min; HD 5.0 ± 0.8 l/min; p < 0.001), heart rate (placebo 3.3 ± 1.0 beats/min; LD 8.8 ± 1.8 beats/min; HD 17.8 ± 2.1 beats/min; p < 0.001), and left ventricular ejection fraction (placebo 0.6 ± 1.4%; LD 6.6 ± 1.5%; HD 14.1 ± 0.8%; p < 0.001) while decreasing systemic vascular resistance (placebo −128 ± 50 dynes·s/cm5; LD −407 ± 49 dynes·s/cm5; HD −774 ± 133 dynes·s/cm5; p < 0.001). Activation of plasma renin activity (p = 0.002), angiotensin II (p = 0.001), and norepinephrine (p < 0.001) occurred only with the higher 100-μg dose. Subtle decreases in urine volume (p = 0.012) and natriuresis (p = 0.001) were observed.ConclusionsBrief intravenous infusions of UCN 2 in healthy humans induced pronounced dose-related increases in cardiac output, heart rate, and left ventricular ejection fraction while decreasing systemic vascular resistance. Subtle renal effects and activation of plasma renin, angiotensin II, and norepinephrine (at high-dose only) were observed. These findings warrant further investigation of the role of UCN 2 in circulatory regulation and its potential therapeutic application in heart disease

Following Natures Lead: On the Construction of Membrane-Inserted Toxins in Lipid Bilayer Nanodiscs

Bacterial toxin or viral entry into the cell often requires cell surface binding and endocytosis. The endosomal acidification induces a limited unfolding/refolding and membrane insertion reaction of the soluble toxins or viral proteins into their translocation competent or membrane inserted states. At the molecular level, the specific orientation and immobilization of the pre-transitioned toxin on the cell surface is often an important prerequisite prior to cell entry. We propose that structures of some toxin membrane insertion complexes may be observed through procedures where one rationally immobilizes the soluble toxin so that potential unfolding ↔ refolding transitions that occur prior to membrane insertion orientate away from the immobilization surface in the presence of lipid micelle pre-nanodisc structures. As a specific example, the immobilized prepore form of the anthrax toxin pore translocon or protective antigen can be transitioned, inserted into a model lipid membrane (nanodiscs), and released from the immobilized support in its membrane solubilized form. This particular strategy, although unconventional, is a useful procedure for generating pure membrane-inserted toxins in nanodiscs for electron microscopy structural analysis. In addition, generating a similar immobilized platform on label-free biosensor surfaces allows one to observe the kinetics of these acid-induced membrane insertion transitions. These platforms can facilitate the rational design of inhibitors that specifically target the toxin membrane insertion transitions that occur during endosomal acidification. This approach may lead to a new class of direct anti-toxin inhibitors

Constructing Kinetically Controlled Denaturation Isotherms of Folded Proteins Using Denaturant-Pulse Chaperonin Binding

Methods to assess the kinetic stability of proteins, particularly those that are aggregation prone, are very useful in establishing ligand induced stabilizing effects. Because aggregation prone proteins are by nature difficult to work with, most solution based methods are compromised by this inherent instability. Here, we describe a label-free method that examines the denaturation of immobilized proteins where the dynamic unfolded protein populations are captured and detected by chaperonin binding