2,766 research outputs found

    Designing an Empathetic Chatbot and Exploring the Impact of Medium in its Experience and Adoption

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    Grounded in the user experience driven innovation (UXDI) framework (Djamasbi and Strong, 2019), we developed an empathetic chatbot, ERIN, to help college students find resources about sensitive issues such as mental health and Title IX. This extended abstract: 1) Reports ERIN’s UX driven iterative design process, 2) investigates possible influence of medium on ERIN’s user experience, and 3) explores UX factors impacting adoption behavior

    Utilizing pHluorin-Tagged Receptors to Monitor Subcellular Localization and Trafficking

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    Understanding membrane protein trafficking, assembly, and expression requires an approach that differentiates between those residing in intracellular organelles and those localized on the plasma membrane. Traditional fluorescence-based measurements lack the capability to distinguish membrane proteins residing in different organelles. Cutting edge methodologies transcend traditional methods by coupling pH-sensitive fluorophores with total internal reflection fluorescence microscopy (TIRFM). TIRF illumination excites the sample up to approximately 150 nm from the glass-sample interface, thus decreasing background, increasing the signal to noise ratio, and enhancing resolution. The excitation volume in TIRFM encompasses the plasma membrane and nearby organelles such as the peripheral ER. Superecliptic pHluorin (SEP) is a pH sensitive version of GFP. Genetically encoding SEP into the extracellular domain of a membrane protein of interest positions the fluorophore on the luminal side of the ER and in the extracellular region of the cell. SEP is fluorescent when the pH is greater than 6, but remains in an off state at lower pH values. Therefore, receptors tagged with SEP fluoresce when residing in the endoplasmic reticulum (ER) or upon insertion in the plasma membrane (PM) but not when confined to a trafficking vesicle or other organelles such as the Golgi. The extracellular pH can be adjusted to dictate the fluorescence of receptors on the plasma membrane. The difference in fluorescence between TIRF images at neutral and acidic extracellular pH for the same cell corresponds to a relative number of receptors on the plasma membrane. This allows a simultaneous measurement of intracellular and plasma membrane resident receptors. Single vesicle insertion events can also be measured when the extracellular pH is neutral, corresponding to a low pH trafficking vesicle fusing with the plasma membrane and transitioning into a fluorescent state. This versatile technique can be exploited to study localization, expression, and trafficking of membrane proteins

    Pharmacological chaperoning of nAChRs: A therapeutic target for Parkinson's disease

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    Chronic exposure to nicotine results in an upregulation of neuronal nicotinic acetylcholine receptors (nAChRs) at the cellular plasma membrane. nAChR upregulation occurs via nicotine-mediated pharmacological receptor chaperoning and is thought to contribute to the addictive properties of tobacco as well as relapse following smoking cessation. At the subcellular level, pharmacological chaperoning by nicotine and nicotinic ligands causes profound changes in the structure and function of the endoplasmic reticulum (ER), ER exit sites, the Golgi apparatus and secretory vesicles of cells. Chaperoning-induced changes in cell physiology exert an overall inhibitory effect on the ER stress/unfolded protein response. Cell autonomous factors such as the repertoire of nAChR subtypes expressed by neurons and the pharmacological properties of nicotinic ligands (full or partial agonist versus competitive antagonist) govern the efficiency of receptor chaperoning and upregulation. Together, these findings are beginning to pave the way for developing pharmacological chaperones to treat Parkinson's disease and nicotine addiction

    Separation of transport lifetimes in SrTi

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    Deviations from Landau Fermi liquid behavior are ubiquitous features of the normal state of unconventional superconductors. Despite several decades of investigation, the underlying mechanisms of these properties are still not completely understood. In this work, we show that two-dimensional electron liquids at SrTiO3/RTiO3 (R = Gd or Sm) interfaces reveal strikingly similar physics. Analysis of Hall and resistivity data show a clear separation of transport and Hall scattering rates, also known as "two-lifetime" behavior. This framework gives a remarkably simple and general description of the temperature dependence of the Hall coefficient. Distinct transport lifetimes accurately describe the transport phenomena irrespective of the nature of incipient magnetic ordering, the degree of disorder, confinement, or the emergence of non-Fermi liquid behavior. The Hall scattering rate diverges at a critical quantum well thickness, coinciding with a quantum phase transition. Collectively, these results introduce new constraints on the existing microscopic theories of lifetime separation and point to the need for unified understanding.Comment: Version accepted for publication in Phys. Rev.

    Estimated Muscle Loads During Squat Exercise in Microgravity Conditions

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    Loss of muscle mass in microgravity is one of the primary factors limiting long-term space flight. NASA researchers have developed a number of exercise devices to address this problem. The most recent is the Advanced Resistive Exercise Device (ARED), which is currently used by astronauts on the International Space Station (ISS) to emulate typical free-weight exercises in microgravity. ARED exercise on the ISS is intended to reproduce Earth-level muscle loads, but the actual muscle loads produced remain unknown as they cannot currently be measured directly. In this study we estimated muscle loads experienced during squat exercise on ARED in microgravity conditions representative of Mars, the moon, and the ISS. The estimates were generated using a subject-specific musculoskeletal computer model and ARED exercise data collected on Earth. The results provide insight into the capabilities and limitations of the ARED machine

    Assembly of the Complex between Archaeal RNase P Proteins RPP30 and Pop5

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    RNase P is a highly conserved ribonucleoprotein enzyme that represents a model complex for understanding macromolecular RNA-protein interactions. Archaeal RNase P consists of one RNA and up to five proteins (Pop5, RPP30, RPP21, RPP29, and RPP38/L7Ae). Four of these proteins function in pairs (Pop5-RPP30 and RPP21–RPP29). We have used nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC) to characterize the interaction between Pop5 and RPP30 from the hyperthermophilic archaeon Pyrococcus furiosus (Pfu). NMR backbone resonance assignments of free RPP30 (25 kDa) indicate that the protein is well structured in solution, with a secondary structure matching that observed in a closely related crystal structure. Chemical shift perturbations upon the addition of Pop5 (14 kDa) reveal its binding surface on RPP30. ITC experiments confirm a net 1 : 1 stoichiometry for this tight protein-protein interaction and exhibit complex isotherms, indicative of higher-order binding. Indeed, light scattering and size exclusion chromatography data reveal the complex to exist as a 78 kDa heterotetramer with two copies each of Pop5 and RPP30. These results will inform future efforts to elucidate the functional role of the Pop5-RPP30 complex in RNase P assembly and catalysis
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