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MIT Open Access Articles
Mostrando recursos 41 - 60 de 14,579
Impact of flow pulsatility on arterial drug distribution in stent-based therapy - O'Brien, Caroline C.; Kolachalama, Vijaya B.; Barber, Tracie J.; Simmons, Anne; Edelman, Elazer R.
Drug-eluting stents reside in a dynamic fluid environment where the extent to which drugs are distributed within the arterial wall is critically modulated by the blood flowing through the arterial lumen. Yet several factors associated with the pulsatile nature of blood flow and their impact on arterial drug deposition have not been fully investigated. We employed an integrated framework comprising bench-top and computational models to explore the factors governing the time-varying fluid dynamic environment within the vasculature and their effects on arterial drug distribution patterns. A custom-designed bench-top framework comprising a model of a single drug-eluting stent strut and a...
Asymmetric Frequency Conversion in Nonlinear Systems Driven by a Biharmonic Pump - Kamal, Archana; Roy, Ananda; Clarke, John; Devoret, Michel H.
A novel mechanism of asymmetric frequency conversion is investigated in nonlinear dispersive devices driven parametrically with a biharmonic pump. When the relative phase between the first and second harmonics combined in a two-tone pump is appropriately tuned, nonreciprocal frequency conversion, either upward or downward, can occur. Full directionality and efficiency of the conversion process is possible, provided that the distribution of pump power over the harmonics is set correctly. While this asymmetric conversion effect is generic, we describe its practical realization in a model system consisting of a current-biased, resistively shunted Josephson junction. Here, the multiharmonic Josephson oscillations, generated internally...
Y[subscript MAP]: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens - Abbey, Darren A; Funt, Jason; Lurie-Weinberger, Mor N; Thompson, Dawn A; Regev, Aviv; Myers, Chad L; Berman, Judith
The design of effective antimicrobial therapies for serious eukaryotic pathogens requires a clear understanding of their highly variable genomes. To facilitate analysis of copy number variations, single nucleotide polymorphisms and loss of heterozygosity events in these pathogens, we developed a pipeline for analyzing diverse genome-scale datasets from microarray, deep sequencing, and restriction site associated DNA sequence experiments for clinical and laboratory strains of Candida albicans, the most prevalent human fungal pathogen. The Y[subscript MAP] pipeline (http://lovelace.cs.umn.edu/Ymap/) automatically illustrates genome-wide information in a single intuitive figure and is readily modified for the analysis of other pathogens with small genomes.
SpaceTop: integrating 2D and spatial 3D interactions in a see-through desktop environment - Lee, Jinha; Olwal, Alex; Ishii, Hiroshi; Boulanger, Cati
SpaceTop is a concept that fuses spatial 2D and 3D interactions in a single workspace. It extends the traditional desktop interface with interaction technology and visualization techniques that enable seamless transitions between 2D and 3D manipulations. SpaceTop allows users to type, click, draw in 2D, and directly manipulate interface elements that float in the 3D space above the keyboard. It makes it possible to easily switch from one modality to another, or to simultaneously use two modalities with different hands. We introduce hardware and software configurations for co-locating these various interaction modalities in a unified workspace using depth cameras and...
Second surface: multi-user spatial collaboration system based on augmented reality - Kasahara, Shunichi; Heun, Valentin Markus Josef; Lee, Austin S.; Ishii, Hiroshi
An environment for creative collaboration is significant for enhancing human communication and expressive activities, and many researchers have explored different collaborative spatial interaction technologies. However, most of these systems require special equipment and cannot adapt to everyday environment. We introduce Second Surface, a novel multi-user Augmented reality system that fosters a real-time interaction for user-generated contents on top of the physical environment. This interaction takes place in the physical surroundings of everyday objects such as trees or houses. Our system allows users to place three dimensional drawings, texts, and photos relative to such objects and share this expression with any...
Modeling the Dynamics of Nonverbal Behavior on Interpersonal Trust for Human-Robot Interactions - Lee, Jin Joo; Knox, Brad; Breazeal, Cynthia Lynn
We describe research towards creating a computational model for recognizing interpersonal trust in social interactions. We found that four negative gestural cues—leaning-backward, face-touching, hand-touching, and crossing-arms—are together predictive of lower levels of trust. Three positive gestural cues—leaning-forward, having arms-in-lap, and open-arms—are predictive of higher levels of trust. We train a probabilistic graphical model using natural social interaction data, a “Trust Hidden Markov Model” that incorporates the occurrence of these seven important gestures throughout the social interaction. This Trust HMM predicts with 69.44% accuracy whether an individual is willing to behave cooperatively or uncooperatively with their novel partner; in comparison, a...
Drug discovery: A jump-start for electroceuticals - Famm, Kristoffer; Litt, Brian; Tracey, Kevin J.; Boyden, Edward Stuart; Slaoui, Moncef
Imagine a day when electrical impulses are a mainstay of medical treatment. Your clinician will administer electroceuticals that target individual nerve fibres or specific brain circuits to treat an array of conditions. These will modulate the neural impulses that control the body, repair lost function and reinstate a healthy balance. They could coax insulin from islet cells, regulate food intake, and control inflammation. They may treat pressing major ailments such as hypertension, diabetes, obesity, heart failure, pulmonary and vascular disease. All this is within reach, we argue, if researchers from disparate disciplines in academia and industry work together. We herewith...
In vivo robotics: the automation of neuroscience and other intact-system biological fields - Forest, Craig R.; Kodandaramaiah, Suhasa Bangalo; Boyden, Edward Stuart
Robotic and automation technologies have played a huge role in in vitro biological science, having proved critical for scientific endeavors such as genome sequencing and high-throughput screening. Robotic and automation strategies are beginning to play a greater role in in vivo and in situ sciences, especially when it comes to the difficult in vivo experiments required for understanding the neural mechanisms of behavior and disease. In this perspective, we discuss the prospects for robotics and automation to influence neuroscientific and intact-system biology fields. We discuss how robotic innovations might be created to open up new frontiers in basic and applied...
Phase-noise limitations on single-photon cross-phase modulation with differing group velocities - Shapiro, Jeffrey H.; Dove, Justin Michael; Chudzicki, Christopher Alan
A framework is established for evaluating cphase gates that use single-photon cross-phase modulation (XPM) originating from the Kerr nonlinearity. Prior work [J. H. Shapiro, Phys. Rev. A 73, 062305 (2006)], which assumed that the control and target pulses propagated at the same group velocity, showed that the causality-induced phase noise required by a noninstantaneous XPM response function precluded the possibility of high-fidelity π-radian conditional phase shifts. The framework presented herein incorporates the more realistic case of group-velocity disparity between the control and target pulses, as employed in existing XPM-based fiber-optical switches. Nevertheless, the causality-induced phase noise identified by Shapiro [J....
An Arp2/3 Nucleated F-Actin Shell Fragments Nuclear Membranes at Nuclear Envelope Breakdown in Starfish Oocytes - Mori, Masashi; Kondo, Hiroshi; Monnier, Nilah; Falk, Henning J.; Machado, Pedro; Bathe, Mark; Somogyi, Kalman; Nedelec, Francois; Lenart, Peter
Animal cells disassemble and reassemble their nuclear envelopes (NEs) upon each division. Nuclear envelope breakdown (NEBD) serves as a major regulatory mechanism by which mixing of cytoplasmic and nuclear compartments drives the complete reorganization of cellular architecture, committing the cell for division. Breakdown is initiated by phosphorylation-driven partial disassembly of the nuclear pore complexes (NPCs), increasing their permeability but leaving the overall NE structure intact. Subsequently, the NE is rapidly broken into membrane fragments, defining the transition from prophase to prometaphase and resulting in complete mixing of cyto- and nucleoplasm. However, the mechanism underlying this rapid NE fragmentation remains largely...
Quantifying Cell-to-Cell Variation in Power-Law Rheology - Cai, PingGen; Mizutani, Yusuke; Tsuchiya, Masahiro; Maloney, John M.; Fabry, Ben; Van Vliet, Krystyn J.; Okajima, Takaharu; Maloney, John M.; Van Vliet, Krystyn J.
Among individual cells of the same source and type, the complex shear modulus G[subscript ∗] exhibits a large log-normal distribution that is the result of spatial, temporal, and intrinsic variations. Such large distributions complicate the statistical evaluation of pharmacological treatments and the comparison of different cell states. However, little is known about the characteristic features of cell-to-cell variation. In this study, we investigated how this variation depends on the spatial location within the cell and on the actin filament cytoskeleton, the organization of which strongly influences cell mechanics. By mechanically probing fibroblasts arranged on a microarray, via atomic force microscopy,...
Urban characteristics attributable to density-driven tie formation - Pan, Wei; Ghoshal, Gourab; Krumme, Coco; Cebrian, Manuel; Pentland, Alex Paul
Motivated by empirical evidence on the interplay between geography, population density and societal interaction, we propose a generative process for the evolution of social structure in cities. Our analytical and simulation results predict both super-linear scaling of social-tie density and information contagion as a function of the population. Here we demonstrate that our model provides a robust and accurate fit for the dependency of city characteristics with city-size, ranging from individual-level dyadic interactions (number of acquaintances, volume of communication) to population level variables (contagious disease rates, patenting activity, economic productivity and crime) without the need to appeal to heterogeneity, modularity,...
Dysfunctional endothelial cells directly stimulate cancer inflammation and metastasis - Franses, Joseph W.; Drosu, Natalia C.; Gibson, William J.; Chitalia, Vipul C.; Edelman, Elazer R.
Although the influence of context-dependent endothelial cell (EC) regulation of vascular disease and repair is well-established, the privileged roles ECs play as paracrine regulators of tumor progression has only recently become appreciated. We hypothesized that if the same endothelial physiology governs vascular and cancer biology then EC control in cancer should follow endothelial regulation of vascular health. Healthy ECs promote vascular repair and inhibit tumor invasiveness and metastasis. Dysfunctional ECs have the opposite effects in vascular disease, and we now ask if dysfunctionally activated ECs will promote cancer cell inflammatory signaling and aggressive properties. Indeed, while factors released from quiescent...
Acetate metabolism in cancer cells - Hosios, Aaron M; Vander Heiden, Matthew G.
Macromolecule biosynthesis is required to duplicate cell components and support proliferation. Studies examining the nutrients used by cancer cells have focused on the contribution of glucose and glutamine carbon for biosynthesis, but the importance of other metabolic fuels is becoming apparent. Labeling of two-carbon units in newly synthesized lipids has been used to infer the nutrients that contribute to the acetyl-CoA pools in cells. Glucose- and glutamine-derived carbon are known to contribute extensively to de novo lipid biosynthesis, and in this issue Kamphorst et al. find that extracellular acetate can also contribute substantially to this process .
Methodology for analysis of TSV stress induced transistor variation and circuit performance - Yu, Li; Chang, Wen-Yao; Zuo, Kewei; Wang, Jean; Yu, Douglas; Boning, Duane S.
As continued scaling becomes increasingly difficult, 3D integration with through silicon vias (TSVs) has emerged as a viable solution to achieve higher bandwidth and power efficiency. Mechanical stress induced by thermal mismatch between TSVs and the silicon bulk arising during wafer fabrication and 3D integration, is a key constraint. In this work, we propose a complete flow to characterize the influence of TSV stress on transistor and circuit performance. First, we analyze the thermal stress contour near the silicon surface with single and multiple TSVs through both finite element analysis (FEA) and linear superposition methods. Then, the biaxial stress is...
Weight and volume changing device with liquid metal transfer - Niiyama, Ryuma; Yao, Lining; Ishii, Hiroshi
This paper presents a weight-changing device based on the transfer of mass. We chose liquid metal (Ga-In-Tin eutectic) and a bi-directional pump to control the mass that is injected into or removed from a target object. The liquid metal has a density of 6.44g/cm3, which is about six times heavier than water, and is thus suitable for effective mass transfer. We also combine the device with a dynamic volume-changing function to achieve programmable mass and volume at the same time. We explore three potential applications enabled by weight-changing devices: density simulation of different materials, miniature representation of planets with scaled...
Onset of heterogeneity in culture-expanded bone marrow stromal cells - Whitfield, Matthew J.; Lee, Wong Cheng J.; Van Vliet, Krystyn J.
Inconsistencies among in vitro and in vivo experiments using adult mesenchymal stem cells (MSCs) confound development of therapeutic, regenerative medicine applications, and in vitro expansion is typically required to achieve sufficient cell numbers for basic research or clinical trials. Though heterogeneity in both morphology and differentiation capacity of culture-expanded cells is noted, sources and consequences are not well understood. Here, we endeavored to observe the onset of population heterogeneity by conducting long-term continuous in vitro observation of human adult bone marrow stromal cell (BMSC) populations, a subset of which has been shown to be stem cells (also known as bone...
Effects of Spanwise Flexibility on Lift and Rolling Moment of a Wingsail - Widnall, Sheila E.; Cornwell, Hayden K.; Williams, Peter J.
Several authors have considered the optimization of spanwise loading on a wing, subject to different constraints. Jones (1) calculated the optimum spanwise lift distribution for a wing subject to a constraint on lift and root bending moment. Tan and Wood (2) applied these ideas to determine the optimum spanwise lift distribution for a yacht sail subject to a constraint on the rolling moment while maximizing forward thrust. Subsequent authors, such as Junge et.al. (3) and Sneyd and Sugimoto (4) extended the analysis to include spanwise variation of wind strength and direction and boat heel. All of these analyses confirm the...
Polymer-Based Catch-Bonds - Chen, Hsieh; Alexander-Katz, Alfredo
Catch-bonds refer to the counterintuitive notion that the average lifetime of a bond has a maximum at a nonzero applied force. They have been found in several ligand-receptor pairs and their origin is still a topic of debate. Here, we use coarse-grained simulations and kinetic theory to demonstrate that a multimeric protein, with self-interacting domain pairs, can display catch-bond behavior. Our model is motivated by one of the largest proteins in the human body, the von Willebrand Factor, which has been found to display this behavior. In particular, our model polymer consists of a series of repeating units that self-interact...
Blimp1 Expression Predicts Embryonic Stem Cell Development In Vitro - Chu, Li-Fang; Surani, M. Azim; Jaenisch, Rudolf; Zwaka, Thomas P.
Despite recent critical insights into the pluripotent state of embryonic stem cells (ESCs), there is little agreement over the inaugural and subsequent steps leading to its generation [1, 2, 3 and 4]. Here we show that inner cell mass (ICM)-generated cells expressing Blimp1, a key transcriptional repressor of the somatic program during germ cell specification [5 and 6], emerge on day 2 of blastocyst culture. Single-cell gene expression profiling indicated that many of these Blimp1-positive cells coexpress other genes typically associated with early germ cell specification. When genetically traced in vitro, these cells acquired properties normally associated with primordial germ...