Mapping lung cancer epithelial-mesenchymal transition states and trajectories with single-cell resolution.

Elucidating the spectrum of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in clinical samples promises insights on cancer progression and drug resistance. Using mass cytometry time-course analysis, we resolve lung cancer EMT states through TGFβ-treatment and identify, through TGFβ-withdrawal, a distinct MET state. We demonstrate significant differences between EMT and MET trajectories using a computational tool (TRACER) for reconstructing trajectories between cell states. In addition, we construct a lung cancer reference map of EMT and MET states referred to as the EMT-MET PHENOtypic STAte MaP (PHENOSTAMP). Using a neural net algorithm, we project clinical samples onto the EMT-MET PHENOSTAMP to characterize their phenotypic profile with single-cell resolution in terms of our in vitro EMT-MET analysis. In summary, we provide a framework to phenotypically characterize clinical samples in the context of in vitro EMT-MET findings which could help assess clinical relevance of EMT in cancer in future studies

Big bottlenecks in cardiovascular tissue engineering.

Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges

Modeling of Tunable Elastic Ultralight Aircraft

Aircraft weight is one of the most critical factors in the design and operation of modern vehicles. The ability to integrate ultra-light materials into the primary load bearing structures has the potential to reduce aircraft weight significantly. Ultralight materials tend to be lattice-based meta-materials that are difficult and computationally expensive to model. One of the advantages of meta-materials is to be able to tune or "program" their bulk material properties through the placement of heterogeneous components in the material. A large amount of time devoted to the simulation in the development time for the tuning of the material can be a barrier to the adoption of large scale lattice materials. In this paper, we present a workflow and analysis tool-set to provide first-order estimates for rapid development of engineered lattice materials for aerospace applications. We present results for estimating the displacement and maximum structural stresses

Technology use by people with intellectual and developmental disabilities to support employment activities: A single-subject design meta analysis

This is the published version. Copyright 2006 IOS PressObjectives: Technology has the potential to improve employment and rehabilitation related outcomes for persons with disabilities. The purpose of this study was to examine the impact of technology use on employment-related outcomes for people with intellectual and developmental disabilities. Study design: A comprehensive search of the literature pertaining to technology use by people with intellectual disabilities was conducted, and a single-subject design meta analysis was conducted for a subset of those studies, which focused on employment and rehabilitation related outcomes. Results: The use of technology to promote outcomes in this area was shown to be generally effective, in particular when universal design features were addressed. Conclusions: Technology has the potential to enable people with intellectual and developmental disabilities to achieve more positive employment and rehabilitation outcomes. It is important to focus on universal design features important to persons with cognitive disabilities, and there is a need for more research in this area

The Architecture of the GW Ori Young Triple Star System and Its Disk: Dynamical Masses, Mutual Inclinations, and Recurrent Eclipses

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main sequence hierarchical triple star system GW Ori. A forward-modeling of the ${}^{13}$CO and C${}^{18}$O $J$=2-1 transitions permits a measurement of the total stellar mass in this system, $5.29 \pm 0.09\,M_\odot$, and the circum-triple disk inclination, $137.6 \pm 2.0^\circ$. Optical spectra spanning a 35 year period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a $241.50\pm0.05$ day period; a tertiary companion orbits that inner pair with a $4218\pm50$ day period. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system ($M_\mathrm{A} \approx 2.7\,M_\odot$, $M_\mathrm{B} \approx 1.7\,M_\odot$, $M_\mathrm{C} \approx 0.9\,M_\odot$) and find strong evidence that at least one (and likely both) stellar orbital planes are misaligned with the disk plane by as much as $45^\circ$. A $V$-band light curve spanning 30 years reveals several new $\sim$30 day eclipse events 0.1-0.7~mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB-C orbital period. Taken together, these features suggest that the A-B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is $\sim$1 Myr old.Comment: 26 pages, 15 figures, accepted to Ap

Recent Duplication and Functional Divergence in Parasitic Nematode Levamisole-Sensitive Acetylcholine Receptors

Helminth parasites rely on fast-synaptic transmission in their neuromusculature to experience the outside world and respond to it. Acetylcholine plays a pivotal role in this and its receptors are targeted by a wide variety of both natural and synthetic compounds used in human health and for the control of parasitic disease. The model, Caenorhabditis elegans is characterized by a large number of acetylcholine receptor subunit genes, a feature shared across the nematodes. This dynamic family is characterized by both gene duplication and loss between species. The pentameric levamisole-sensitive acetylcholine receptor has been characterized from C. elegans, comprised of five different subunits. More recently, cognate receptors have been reconstituted from multiple parasitic nematodes that are found to vary in subunit composition. In order to understand the implications of receptor composition change and the origins of potentially novel drug targets, we investigated a specific example of subunit duplication based on analysis of genome data for 25 species from the 50 helminth genome initiative. We found multiple independent duplications of the unc-29, acetylcholine receptor subunit, where codon substitution rate analysis identified positive, directional selection acting on amino acid positions associated with subunit assembly. Characterization of four gene copies from a model parasitic nematode, Haemonchus contortus, demonstrated that each copy has acquired unique functional characteristics based on phenotype rescue of transgenic C. elegans and electrophysiology of receptors reconstituted in Xenopus oocytes. We found evidence that a specific incompatibility has evolved for two subunits co-expressed in muscle. We demonstrated that functional divergence of acetylcholine receptors, driven by directional selection, can occur more rapidly than previously thought and may be mediated by alteration of receptor assembly. This phenomenon is common among the clade V parasitic nematodes and this work provides a foundation for understanding the broader context of changing anthelmintic drug targets across the parasitic nematodes

Müllerian Adenosarcoma of the Urinary Bladder: Clinicopathologic and Immunohistochemical Features with Novel Genetic Aberrations

Müllerian adenosarcoma is a biphasic neoplasm most commonly of the uterus and less frequently of the ovary. It has been rarely described to occur in other sites such as peritoneum and liver. In this study, we report the clinicopathologic, immunohistochemical and molecular features of a primary müllerian adenosarcoma of the urinary bladder in a 62-year-old woman. To our knowledge, this is the first report of müllerian adenosarcoma primary to the urinary bladder in the literature. Light microscopy showed a biphasic epithelial and stromal tumor with benign-appearing glands surrounded by endometrial-type stroma that is densely cellular with increased mitotic figures. The stroma surrounding the glands is more cellular than the intervening areas, which are more loose and edematous. Immunohistochemistry profile included positive staining for Pax2/8 within the glands, for CD10 and WT-1 within the spindled stroma, and for estrogen and progesterone receptors in both. Staining for desmin, GATA3, p63, and human papilloma virus (HPV) is negative. Molecular analyses identified mutations in AKT1 E17K, FLT3 D835N, KRAS G12D and HRAS G12S. These novel molecular aberrations have yet to be reported in the medical literature. X chromosome inactivation analysis revealed a clonal pattern in the stromal component and a non-clonal pattern in the epithelial component. Currently, the patient is disease/recurrence-free after regular follow-up of approximately 84 months. This case represents the first reported diagnosis of müllerian adenosarcoma arising in the urinary bladder with extensive clinicopathologic, immunohistochemical, and molecular analyses

Trusting Robocop: Gender-Based Effects on Trust of an Autonomous Robot

Little is known regarding public opinion of autonomous robots. Trust of these robots is a pertinent topic as this construct relates to one’s willingness to be vulnerable to such systems. The current research examined gender-based effects of trust in the context of an autonomous security robot. Participants (N = 200; 63% male) viewed a video depicting an autonomous guard robot interacting with humans using Amazon’s Mechanical Turk. The robot was equipped with a non-lethal device to deter non-authorized visitors and the video depicted the robot using this non-lethal device on one of the three humans in the video. However, the scenario was designed to create uncertainty regarding who was at fault – the robot or the human. Following the video, participants rated their trust in the robot, perceived trustworthiness of the robot, and their desire to utilize similar autonomous robots in several different contexts that varied from military use to commercial use to home use. The results of the study demonstrated that females reported higher trust and perceived trustworthiness of the robot relative to males. Implications for the role of individual differences in trust of robots are discussed

The heat-stable cytosolic factor that promotes glucocorticoid receptor binding to DNA is neither thioredoxin nor ribonuclease

Treatment of rat liver cytosol containing temperature-transformed [3H]dexamethasone-bound receptors at 0[deg]C with the sulfhydryl modifying reagent methyl methanethiosulfonate (MMTS) inhibits the DNA-binding activity of the receptor, and DNA-binding activity is restored after addition of dithiothreitol (DTT). However, transformed receptors that are treated with MMTS and then separated from low Mr components of cytosol by passage through a column of Sephadex G-50 have very little DNA-binding activity when DTT is added to regenerate sulfhydryl moities. The receptors will bind to DNA if whole liver cytosol or boiled liver cytosol is added in addition to DTT. The effect of boiled cytosol is mimicked by purified rat thioredoxin or bovine RNase A in a manner that does not reflect the reducing activity of the former or the catalytic activity of the latter. This suggests that the reported ability of each of these heat-stable peptides to stimulate DNA binding by glucocorticoid receptors is not a biologically relevant action. We suggest that stimulation of DNA binding of partially purified receptors by boiled cytosol does not constitute a reconstitution of a complete cytosolic system in which the dissociated receptor must associate with a specific heat-stable accessory protein required for DNA binding, as has been suggested in the "two-step" model of receptor transformation recently proposed by Schmidt et al.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26525/1/0000064.pd