Dartmouth Institute for Health Policy and Clinical Practice
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Contextualizing Interpersonal Data Sharing in Smart Homes
Get PDFA key feature of smart home devices is monitoring the environment and recording data. These devices provide security via motion-detection video alerts, cost-savings via thermostat usage history, and peace of mind via functions like auto-locking doors or water leak detectors. At the same time, the sharing of this information in interpersonal relationships---though necessary---is currently accomplished on an all-or-nothing basis. This can easily lead to oversharing in a multi-user environment. Although prior work has studied people\u27s perceptions of information sharing with vendors or ISPs, the sharing of household data among users who interact personally is less well understood. Interpersonal situations make data sharing much more context-based and, thus, more complicated. In this paper, we use themes from the theory of contextual integrity in an online survey (n=1,992) to study how people perceive data sharing with others in smart homes and inform future designs and research. Our results show that data recipients in a smart home can be reduced to three major groups, and data types matter more than device types. We also found that the types of access control desired by users can vary from scenario to scenario. Depending on whom they are sharing data with and about what data, participants expressed varying levels of comfort when presented with different types of access control (e.g., explicit approval versus time-limited access). Taken together, this provides strong evidence that a more dynamic access control system is needed, and we can design it in a more usable way
Design, Analysis, and Drop Assembly of Interlocking Rigid Bodies
Get PDFThis work presents a system of interlocking blocks that can be used to build a wide variety of structures. The blocks slide together to form structures that interlock geometrically like a puzzle to form semi-permanent structures without the need for cement or friction lock. The blocks are designed to be easy to fabricate, assemble, and disassemble. Contributions of the block designs include a novel interlocking joint structure; the joints are wedge-shaped, allowing for error mitigation during assembly and allowing structures to be assembled without jamming even if there is manufacturing error. We introduce planar, 3D, and volumetric designs using these wedge-shaped joints. Additionally, this work introduces two formalized models of interlock and provides analysis methods for both models to test if structures are interlocked. This work also expands a planar framework for the analysis of free motions and aggregate flexibility of loose chains, and adapts the analysis for the specific application of interlock. Additionally, an extension of this analysis into 3D is introduced and applied to interlocking structures. We demonstrate how this analysis can be used to optimize the design of individual block geometries, as well as the layout of the complete structure. We demonstrate robot assembly of systems of blocks using a simple and rather imprecise robot arm to build structures under an open-loop model of assembly, and provide additional examples of larger-scale, hand-built interlocking structures
Random Walk Methods for Geometry Representation Agnostic Transport
Get PDFIn computer graphics, we use geometry representations to model a wide range of virtual scenes—from the fantastical worlds shown in animated movies to intricate mechanical parts.These representations provide the context for transport problems—light transport is used to produce images of virtual scenes and diffusive transport to simulate distributions of quantities like heat.There are many types of representations each with their own advantages.For example, explicit ones make it easy to directly manipulate surfaces, while implicit representations allow for intuitive modeling by non-technical users and straightforward integration into machine learning systems.Unfortunately, many algorithms that work on these digital scenes make strong assumptions on the information the representation is able to provide.This causes interoperability issues—geometry has to be lossily converted while being passed from one method to the next.Our goal is to develop transport methods agnostic of the underlying geometry representation.We first extend the surface editing capabilities of implicit surfaces—bringing them closer to explicit representations—and recognize that systems used in practice already favor algorithms agnostic of the underlying representation.We then pose that random walk algorithms for transport use a minimal geometry API that can be easily supported by a wide range of representations.Light transport has long been primarily solved by such random walk methods, but diffusive transport solvers on the other hand have been focused on finite element methods which require an explicit representation of the scene.We provide a unified view of radiative and diffusive transport and use it to extend the field of random walk methods for diffusive transport.Beyond simulating transport, stochastic processes are also used to model microscopic irregularities in the geometry of the scene—resulting in models for rough surfaces and participating media. Transport can then be computed as the ensemble average over all realizations of a process, but explicit representation of realizations is intractable. By using geometry agnostic random walk methods we can compute the ensemble averaged transport on the stochastic implicit representation directly, allowing us to use stochastic geometry as a new geometry representation that seamlessly transitions between surface and volume models
FleQ and Gac/Rsm-Mediated Regulation of Biofilm Formation and Swarming Motility in Pseudomonas fluorescens
Get PDFPseudomonas fluorescens is a gram-negative Gammaproteobacterium that survives and persists in diverse environments. This survivability is dependent on the bacterium’s ability to form a biofilm. Within Pseudomonas fluorescens, biofilm formation is a complex and dynamic process involving multiple protein- and polysaccharide-based components which each individually serve a specific purpose. Of these components, the repeats-in-toxin (RTX) adhesins LapA and MapA are critical for biofilm formation. Specifically, LapA is important for initial establishment of a biofilm and MapA is important in forming a fully mature biofilm. Deployment of the RTX adhesins during biofilm formation is a highly coordinated process involving multiple transcriptional, post-transcriptional, and post-translation mechanisms. For the transcriptional regulator FleQ, it has been previously shown that FleQ and the Gac/Rsm pathway both impact biofilm formation. However, it is currently unclear which biofilm components are regulated by these regulators.
In this thesis, I show that FleQ both transcriptionally and post-transcriptionally regulates the RTX adhesins. I provide evidence that FleQ directly regulates lapA and mapA RNA levels. Additionally, we determined that the regulation of LapA and MapA protein levels is mediated by the Gac/Rsm pathway. I further show that this regulation is specifically mediated by the small regulatory protein RsmE and the small regulatory RNA rsmZ.
While it was previously thought that Gac/Rsm pathway in the Pseudomonas fluorescens Pf0-1 strain was completely non-function due to a point mutation in GacA, I demonstrated through overexpression of the GacS histidine kinase that the Gac/Rsm pathway in the Pseudomonas fluorescens Pf0-1 strain is functional but attenuated compared to other lab strains. I additionally showed that this strain deploys the biosurfactant Gacamide A and swarms in an RsmA- and RsmE-dependent manner. Through mutagenic studies, I provide evidence that the proteins encoded by the pleABC operon secrete Gacamide A. I then demonstrate that multiple pathways regulate swarming motility by regulating flagellar function or biosurfactant deployment.
Collectively, the work in this thesis provides additional mechanistic insight into how FleQ and the Gac/Rsm pathway regulate biofilm formation and swarming motility
Cytokine activity estimation and receptor abundance approximation with multimodal scRNA-seq/CITE-seq data.
No full textSingle-cell RNA-sequencing (scRNA-seq) data enables individual cell resolution quantification of messenger RNA. While revolutionary for revealing key cell type and cell phenotype-specific heterogeneity, scRNA-seq data has important statistical challenges. First, scRNA-seq data is usually more sparse and second, it is more variable than bulk transcriptomics data. Given these challenges, more intuitive and interpretive statistical and computational methods are needed to develop appropriate solutions. Here, we detail the development of three techniques to perform receptor abundance estimation and cytokine activity estimation for scRNA-seq data. While SPECK (Surface Protein abundance Estimation using CKmeans-based clustered thresholding) and STREAK (gene Set Testing-based Receptor abundance Estimation using Adjusted distances and cKmeans thresholding) methods address the sparsity constraints of scRNA-seq data via dimensionality reduction and a thresholding mechanism and co-expression analysis using joint scRNA-seq/CITE-seq data, respectively, SCAPE (Single cell transcriptomics-level Cytokine Activity Prediction and Estimation) aims to leverage a cytokine signaling activity database via a modified gene set testing approach to accommodate negative weights. Our approaches work well in practice and aim to provide more interpretive solutions to statistical challenges of scRNA-seq data. Furthermore, our methods have the potential to be integrated in bioinformatics pipelines for the tasks of cell type and cell state identification
The Large-scale Environments of Active Galactic Nuclei
Get PDFIt is now recognized that the energy released by accreting supermassive black holes observed as Active Galactic Nuclei (AGN) is integral in shaping the dynamics of baryons on up to cosmological scales, and AGN thus play a significant role in regulating the formation and evolution of galaxies. Studying the clustering properties of AGN reveals which environments they release this feedback energy into, testing models of AGN-galaxy coevolution and AGN structure. In this thesis, I leverage wide-area photometric and spectroscopic survey data to measure the clustering properties of various AGN samples containing millions of systems, placing tight constraints on the properties of their host dark matter halos. I first investigate the host halo properties of optically-selected red and blue quasars, finding no significant difference in their environments. Thus, quasars buried under mild dust columns likely do not represent a special phase of AGN-galaxy coevolution. On the other hand, I show that heavily obscured infrared-selected quasars occupy systematically more massive halos than their unobscured counterparts, suggesting that obscured quasars may represent a special phase of AGN-galaxy coevolution in which the black hole and galaxy are fed by common gas streams. Finally, I show that luminous low-frequency radio galaxies are hosted by massive galaxy groups over cosmic time, implying that jet-mode feedback dominates over quasar wind-mode feedback in groups and clusters
Near-Infrared Paired-Agent Imaging for In Vivo Quantification of Receptor Occupancy in Tumor
No full textAccurate assessment of drug receptor occupancy (RO) holds significant importance in both drug development and personalized medicine, as it facilitates quantitative characterization of dose-response relationship for a given drug. This information not only aids appropriate dose selection for clinical trials but also guides personalized dose optimization in precision medicine.
Molecular imaging, utilizing receptor-specific imaging agents for tissue visualization, has emerged as the major option for in vivo measurement of tissue RO. Nonetheless, the abnormal yet complex structure and hemodynamics of tumors often lead to substantial non-specific uptake and retention of imaging agents, thus introducing significant bias to RO measurements. To address the challenge, a quantitative molecular imaging strategy known as near-infrared paired-agent imaging (PAI) has been developed and characterized. PAI employs simultaneous administration of one receptor-specific imaging agent and a pharmacokinetically similar reference agent devoid of receptor specificity. Through quantification of tumor binding potential (BP), a parameter directly proportional to concentration of unbound receptors, PAI holds the potential to accurately measure tumor RO in vivo.
This thesis focuses on the development and characterization of in vivo PAI to measure RO in tumor. By assessing the receptor binding characteristics of ABY-029, an epidermal growth factor receptor (EGFR)-specific imaging agent, the study revealed ABY-029\u27s potential to reflect drug engagement in tumor. Characterization of pre-drug BP in mouse tumor xenografts imaged with different doses of ABY-029 reconfirmed the independence of BP from ABY-029 dosage. Furthermore, in vivo PAI managed to detect dynamic decrease in tumor BP following drug administration. Subsequent in vivo RO dose studies revealed a dose-dependent increase in tumor RO measured by PAI, highlighting its capability to assess RO in tumors. However, overestimation of tumor BP was also observed. To address this issue, a novel assay was developed and employed to characterize tissue biodistribution of the paired agents in response to drug administration. The analysis identified liver as a major body compartment influencing tumor BP. Further refinement of the compartmental modeling for PAI is thus anticipated to allow accurate BP and RO correction. Nevertheless, this study revealed the promising potential of PAI for both future drug development and precision medicine
Healthcare utilization associated with mental health symptoms in young adults with type 1 diabetes
No full textToday, as mental health illnesses such as depression, anxiety, and eating disorders continue to expand, they are further associated with poor glycemic control, decreased quality of life, increased unemployment, and worse self-care. This study aims to describe the relationship between psychological and diabetes distress and emergency healthcare utilization including 911 calls, ED visits, and hospitalizations among young adults with T1D. The collected and analyzed data indicate that T1D-related ED visits and hospitalizations are significantly associated with higher levels of mental health symptoms and diabetes distress in young adults. In contrast, no significant relationships were found between T1D-related 911 calls and mental health symptoms or diabetes distress.https://digitalcommons.dartmouth.edu/wetterhahn_2024/1004/thumbnail.jp
Role of SDS-22/PP1 phosphatase in polarizing the germplasm of Caenorhabditis elegans embryo
Get PDFDuring asymmetric cell division, cell polarity and cell cycle are tightly coupled to ensure robust segregation of cell fate determinants and generation of cellular diversity. In the one-cell C. elegans embryo, multiple cell cycle kinases regulate cell polarization and posterior segregation of germline fate determinants (germplasm). For example, PLK-1 kinase inhibits the retention of its germplasm substrate POS-1 in the anterior, driving POS-1 segregation to the posterior (Han et al., 2018). Additionally, MBK-2 kinase disassembles P granules in the anterior through phosphorylation of the P granule scaffold MEG-3, helping to drive P granule segregation to the posterior (Wang et al., 2014). However, the equally exciting role of cell cycle phosphatases has been less explored. Recently, two classes of phosphatases PP1 and PP2A-B56, were shown to regulate cell polarity. PP1 promotes PAR-2 dephosphorylation and asymmetric cortical loading (Calvi et al., 2022). PP2A-B56 counteracts MBK-2 by dephosphorylating MEG-3 and favoring its assembly in the posterior (Wang et al., 2014).
Using a combination of genetics and microscopy techniques my work has uncovered a new role for PP1 phosphatase and its regulator SDS-22 in polarizing the germplasm in the C. elegans embryo. In sds-22(RNAi)embryos, germplasm proteins POS-1 and PIE-1 are retained properly in the posterior. Additionally, many P granule proteins fail to stably form granules in the sds-22(RNAi) embryos, suggesting that SDS-22 is critical for global germplasm organization. Indeed, my work provides evidence that SDS-22 downregulates PLK-1 kinase activity and possibly upregulates PP2A-B56 phosphatase activity to promote germplasm retention. First, PLK-1 activity-dependent processes are exaggerated in sds-22(RNAi) embryos. Second, inhibition of PLK-1 activity partially rescues germplasm organization, suggesting that SDS-22 might be downregulating PLK-1 activity. We also show genetic evidence indicating that PP1 binding motif on PP2A-B56 is necessary for its ability to stabilize granules. Finally, I also assessed the dynamics of PLK-1 anterior-rich gradient formation, an event critical for its downstream regulation of germplasm, collaboratively. My thesis contributes to the growing understanding of the coupling between cell cycle and cell polarity
The Hole, the Lake, and the Mountain—Encouraging Insight, Wisdom, and Awareness: The Emerging Concept of Lightenment™
Get PDFABSTRACT
This thesis deals with the possibility that the emerging concept of Major Mindful Moments — Lightenment™ — could further drive mindfulness from a tangential activity to a more central societal concept. I coin Lightenment™, an arising wisdom related to the mindful state as a thought process that positively affects people\u27s happiness and lessens suffering and changes how they interact and behave in the world. These changes, on a broad scale, affect culture and influence the world. Enlightenment, a concept that dates back thousands of years, is a state of continuing wisdom as opposed to Lightenment™ \u27s intermittent wisdom. I explain the benefit of accessibility of Lightenment™ to the non-monastic. For the paper, I use the unique format of Scholarly Personal Narrative (SPN) (Nash, 2011), academic writing that incorporates personal experience as well as scholarly references. To accompany the written text, I include three videocasts—stories which include interviews of guests\u27 experience with a Lightenment™ moment and benefits. In similar fashion to others\u27 experience presented in the videocasts, this paper contains my story of a journey in discovering mindfulness and Lightenment™ to enhance wellbeing and life circumstances. These stories demonstrate that individual experience can ripple out into the collective to address current floundering political, social, environmental, and cultural attempts to create social justice and wellbeing