Declining Burden of Plasmodium vivax in a Population in Northwestern Thailand from 1995 to 2016 before Comprehensive Primaquine Prescription for Radical Cure.

All Plasmodium cases have declined over the last decade in northwestern Thailand along the Myanmar border. During this time, Plasmodium vivax has replaced Plasmodium falciparum as the dominant species. The decline in P. falciparum has been shadowed by a coincidental but delayed decline in P. vivax cases. This may be due to early detection and artemisinin-based therapy, species-specific diagnostics, and bed net usage all of which reduce malaria transmission but not P. vivax relapse. In the absence of widespread primaquine use for radical cure against P. vivax hypnozoites, the decline in P. vivax may be explained by decreased hypnozoite activation of P. vivax relapses triggered by P. falciparum. The observed trends in this region suggest a beneficial effect of decreased P. falciparum transmission on P. vivax incidence, but elimination of P. vivax in a timely manner likely requires radical cure

Computational optimization of gas compressor stations: MINLP models versus continuous reformulations

When considering cost-optimal operation of gas transport networks, compressor stations play the most important role. Proper modeling of these stations leads to nonconvex mixed-integer nonlinear optimization problems. In this article, we give an isothermal and stationary description of compressor stations, state MINLP and GDP models for operating a single station, and discuss several continuous reformulations of the problem. The applicability and relevance of different model formulations, especially of those without discrete variables, is demonstrated by a computational study on both academic examples and real-world instances. In addition, we provide preliminary computational results for an entire network.German Federal Ministry of Economics and Technolog

Grid Fin Stabilization of the Orion Launch Abort Vehicle

Wind tunnel tests were conducted by Nielsen Engineering & Research (NEAR) and Rose Engineering & Research (REAR) in conjunction with the NASA Engineering & Safety Center (NESC) on a 6%-scale model of the Orion launch abort vehicle (LAV) configured with four grid fins mounted near the base of the vehicle. The objectives of these tests were to 1) quantify LAV stability augmentation provided by the grid fins from subsonic through supersonic Mach numbers, 2) assess the benefits of swept grid fins versus unswept grid fins on the LAV, 3) determine the effects of the LAV abort motors on grid fin aerodynamics, and 4) generate an aerodynamic database for use in the future application of grid fins to small length-to-diameter ratio vehicles similar to the LAV. The tests were conducted in NASA Ames Research Center's 11x11-foot transonic wind tunnel from Mach 0.5 through Mach 1.3 and in their 9x7-foot supersonic wind tunnel from Mach 1.6 through Mach 2.5. Force- and moment-coefficient data were collected for the complete vehicle and for each individual grid fin as a function of angle of attack and sideslip angle. Tests were conducted with both swept and unswept grid fins with the simulated abort motors (cold jets) off and on. The swept grid fins were designed with a 22.5deg aft sweep angle for both the frame and the internal lattice so that the frontal projection of the swept fins was the same as for the unswept fins. Data from these tests indicate that both unswept and swept grid fins provide significant improvements in pitch stability as compared to the baseline vehicle over the Mach number range investigated. The swept fins typically provide improved stability as compared to the unswept fins, but the performance gap diminished as Mach number was increased. The aerodynamic performance of the fins was not observed to degrade when the abort motors were turned on. Results from these tests indicate that grid fins can be a robust solution for stabilizing the Orion LAV over a wide range of operating conditions

A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.

Synthetic protein switches controlled with user-defined inputs are powerful tools for studying and controlling dynamic cellular processes. To date, these approaches have relied primarily on intermolecular regulation. Here we report a computationally guided framework for engineering intramolecular regulation of protein function. We utilize this framework to develop chemically inducible activator of RAS (CIAR), a single-component RAS rheostat that directly activates endogenous RAS in response to a small molecule. Using CIAR, we show that direct RAS activation elicits markedly different RAS-ERK signaling dynamics from growth factor stimulation, and that these dynamics differ among cell types. We also found that the clinically approved RAF inhibitor vemurafenib potently primes cells to respond to direct wild-type RAS activation. These results demonstrate the utility of CIAR for quantitatively interrogating RAS signaling. Finally, we demonstrate the general utility of our approach in design of intramolecularly regulated protein tools by applying it to the Rho family of guanine nucleotide exchange factors

Macrostate Data Clustering

We develop an effective nonhierarchical data clustering method using an analogy to the dynamic coarse graining of a stochastic system. Analyzing the eigensystem of an interitem transition matrix identifies fuzzy clusters corresponding to the metastable macroscopic states (macrostates) of a diffusive system. A "minimum uncertainty criterion" determines the linear transformation from eigenvectors to cluster-defining window functions. Eigenspectrum gap and cluster certainty conditions identify the proper number of clusters. The physically motivated fuzzy representation and associated uncertainty analysis distinguishes macrostate clustering from spectral partitioning methods. Macrostate data clustering solves a variety of test cases that challenge other methods.Comment: keywords: cluster analysis, clustering, pattern recognition, spectral graph theory, dynamic eigenvectors, machine learning, macrostates, classificatio

Modulation of Voltage-Gating and Hysteresis of Lysenin Channels by Cu\u3csup\u3e2+\u3c/sup\u3e Ions

The intricate voltage regulation presented by lysenin channels reconstituted in artificial lipid membranes leads to a strong hysteresis in conductance, bistability, and memory. Prior investigations on lysenin channels indicate that the hysteresis is modulated by multivalent cations which are also capable of eliciting single-step conformational changes and transitions to stable closed or sub-conducting states. However, the influence on voltage regulation of Cu2+ ions, capable of completely closing the lysenin channels in a two-step process, was not sufficiently addressed. In this respect, we employed electrophysiology approaches to investigate the response of lysenin channels to variable voltage stimuli in the presence of small concentrations of Cu2+ ions. Our experimental results showed that the hysteretic behavior, recorded in response to variable voltage ramps, is accentuated in the presence of Cu2+ ions. Using simultaneous AC/DC stimulation, we were able to determine that Cu2+ prevents the reopening of channels previously closed by depolarizing potentials and the channels remain in the closed state even in the absence of a transmembrane voltage. In addition, we showed that Cu2+ addition reinstates the voltage gating and hysteretic behavior of lysenin channels reconstituted in neutral lipid membranes in which lysenin channels lose their voltage-regulating properties. In the presence of Cu2+ ions, lysenin not only regained the voltage gating but also behaved like a long-term molecular memory controlled by electrical potentials

Research Weaving: Visualizing the Future of Research Synthesis

We propose a new framework for research synthesis of both evidence and influence, named research weaving. It summarizes and visualizes information content, history, and networks among a collection of documents on any given topic. Research weaving achieves this feat by combining the power of two methods: systematic mapping and bibliometrics. Systematic mapping provides a snapshot of the current state of knowledge, identifying areas needing more research attention and those ready for full synthesis. Bibliometrics enables researchers to see how pieces of evidence are connected, revealing the structure and development of a field. We explain how researchers can use some or all of these tools to gain a deeper, more nuanced understanding of the scientific literature

High-speed camera characterization of voluntary eye blinking kinematics

This is the final version of the article originally published in the Journal of the Royal Society Interface here: http://rsif.royalsocietypublishing.org/content/10/85/20130227.full.pdf+html?sid=65b57db1-37cf-492f-bf3c-b08f2a8c818d.Blinking is vital to maintain the integrity of the ocular surface and its characteristics such as blink duration and speed can vary significantly, depending on the health of the eyes. The blink is so rapid that special techniques are required to characterize it. In this study, a high-speed camera was used to record and characterize voluntary blinking. The blinking motion of 25 healthy volunteers was recorded at 600 frames per second. Master curves for the palpebral aperture and blinking speed were constructed using palpebral aperture versus time data taken from the high-speed camera recordings, which show that one blink can be divided into four phases; closing, closed, early opening and late opening. Analysis of data from the high-speed camera images was used to calculate the palpebral aperture, peak blinking speed, average blinking speed and duration of voluntary blinking and compare it with data generated by other methods previously used to evaluate voluntary blinking. The advantages of the high-speed camera method over the others are discussed, thereby supporting the high potential usefulness of the method in clinical research