Dartmouth Institute for Health Policy and Clinical Practice
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Detecting Battery Cells with Harmonic Radar
No full textHarmonic radar systems have been shown to be an effective method for detecting the presence of electronic devices, even if the devices are powered off. Prior work has focused on detecting specific non-linear electrical components (such as transistors and diodes) that are present in any electronic device. In this paper we show that harmonic radar is also capable of detecting the presence of batteries. We tested a proof-of-concept system on Alkaline, NiMH, Li-ion, and Li-metal batteries. With the exception of Li-metal coin cells, the prototype harmonic radar detected the presence of batteries in our experiments with 100% accuracy
Mechanistic Insights on Positive Regulation of the Pyrin Inflammasome in Macrophages
Get PDFThe mammalian innate immune defense employs sophisticated mechanisms, such as effector triggered immunity (ETI), to discern between pathogenic and non-pathogenic bacteria and initiate a protective response. ETI is involved in immune detection of virulent activities of bacterial effector proteins in the host cytosol. Inflammasome sensors, such as pyrin, detect cellular infection or stress as part of ETI, leading to the assembly of multiprotein complexes, caspase-1 activation and proinflammatory cytokine release. Pyrin uniquely initiates inflammatory responses against RhoA-inactivating bacterial toxins and effectors such as Yersinia\u27s YopE and YopT, and C. difficile’s toxins TcdA/B. Understanding pyrin regulation is crucial due to its association with dysregulated autoinflammatory responses, including Familial Mediterranean Fever (FMF), linked to pyrin gene mutations. Pyrin regulation mirrors the guard hypothesis observed in plants, whereby negative regulation is achieved through phosphorylation by RhoA-PKN signaling and binding of 14-3-3 proteins, maintaining an inactive state. Upon RhoA inactivation, pyrin is dephosphorylated and interacts with the inflammasome adapter protein ASC to assemble a caspase-1 inflammasome. Research into positive regulation mechanisms of pyrin carried out in this dissertation underscores the importance of 1) phosphoserine phosphatase (PPP) activity; 2) oligomerization; and 3) microtubules (MTs) in facilitating inflammasome assembly in phagocytic cells. Murine pyrin is phosphorylated at S205 before inflammasome assembly, and PP2A catalytic subunits dephosphorylate this site in macrophages. Results with Blue-Native (BN)-PAGE show that both human and murine pyrin form dimers and higher-order oligomers which are phosphorylated when inactive. Interestingly, gain of function codon changes associated with autoinflammatory diseases like FMF do not alter steady state oligomerization of human pyrin. Results confirm that intact MTs positively regulate pyrin post-dephosphorylation but upstream of inflammasome assembly. However, MTs do not appear to regulate pyrin oligomerization. Additionally, experiments designed to confirm previous results did not establish a role for the MT-associated protein HDAC6, or localization to MT organizing centers, for murine pyrin inflammasome assembly in macrophages, as shown by live cell imaging. In summary, these findings offer insights into mechanisms of positive regulation of pyrin and a roadmap to further investigate the regulation of oligomeric pyrin and the balance of kinase and phosphatase activity along with MT dynamics in pyrin-associated infectious and autoinflammatory diseases
3-D Reconstruction for Underwater Robots with a Monocular Camera and Lights
Get PDFBefore a robot can act, it must perceive its environment. Though, this is not a simple task when considering the challenges in underwater domains -- poor visibility conditions, limited sensor configurations, and lack of readily accessible localization. Underwater robots have, nevertheless, improved dramatically with more extensive sensor and navigation equipment. Robot and sensor use have enabled us to explore all reaches of our oceans. On the other hand, these same robots are not easily accessible or transferable to many practical tasks, including fishery management, infrastructure maintenance, disaster response, site conservation, and ecological surveys. There is a growing need for robots that are more scalable -- accessible (consisting of off-the-shelf equipment), easy to transport and deploy, and less of a monetary barrier (on the robot and mission). The biggest hurdle is that research on robust perception tools suitable for these scalable robots is still underdeveloped.
This thesis develops methods for improving the 3-D scene reconstruction capability of scalable underwater robots. These robots are modular -- integrated with low-cost sensors, including a monocular camera, multiple lights, a pressure depth sensor, and a single-beam echosounder. Perceiving and modeling complex underwater scenes with a robot requires precise localization, clean and informative sensory data, and a way to recover 3-D scene information. However, this is not directly possible with our simple sensory suite. Dynamic water conditions cause unique image color loss and the air-tight camera enclosures introduce additional image distortions. With only a single camera, vision odometry systems will generate unreliable 3-D scene and localization information. Tools presented throughout this thesis addresses the above challenges. Finally, leading to a novel 3-D scene reconstruction framework that exploits the camera-and-light setup, providing a means to model the unknown scene while simultaneously localizing the robot. Thorough assessments -- in various underwater environments, from controlled scenes in a swimming pool to real-world scenarios in the ocean -- of each tool and final framework validate its importance in underwater perception. This thesis demonstrates the potential and feasibility of scalable underwater robots to undertake challenging perception-based tasks, providing accessible and abundant means for humans to explore and work in the underwater world
PLASMA PER-AND POLYFLUOROALKYL SUBSTANCE (PFAS) MIXTURES AND MATERNAL CARDIOMETABOLIC HEALTH
No full textFood is a common exposure pathway to per- and polyfluoroalkyl substances (PFAS) but dietary factors related to PFAS concentrations in pregnant people have not been adequately evaluated. PFAS have been linked to the increased risk of gestational hypertension, preeclampsia, and adiposity. However, less is known regarding the effect of PFAS mixtures on blood pressure (BP) trajectories in normotensive pregnancies or weight retention postpartum. We used data from the New Hampshire Birth Cohort Study (NHBCS) to examine dietary intake and PFAS concentrations and associations of PFAS with BP trajectories and postpartum weight retention. PFAS concentrations were measured in plasma collected at ~28 weeks gestation and human milk collected at ~6 weeks postpartum. Information on maternal diet was collected using a validated food frequency questionnaire at ~24-28 weeks gestation. BP measurements during pregnancy and pre-pregnancy weight were abstracted from maternal medical records. Self-reported pre-pregnancy weight was used if medical records were unavailable. We calculated the difference between self-reported postpartum weight collected in 2020 and pre-pregnancy weight. Adaptive elastic net was used to identify dietary variables associated with plasma and milk PFAS concentrations while accounting for correlations between dietary variables. Latent class trajectory modeling was used to identify BP trajectory groups among normotensive pregnant people. We used mixture modeling approaches to assess the effect of PFAS mixtures on BP trajectories among normotensive pregnancies and weight change pre-pregnancy to postpartum. We also evaluated whether the PFAS mixtures-weight retention association was modified by pre-pregnancy body mass index. Higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. Plasma PFAS concentrations were associated with greater increases in BP during pregnancy among normotensive people and greater weight retention at ~7 years postpartum for individuals who were obese/overweight pre-pregnancy. Our findings suggest that certain dietary factors during pregnancy influence PFAS concentrations in pregnant people, which can inform interventions to reduce PFAS exposure. Moreover, PFAS may impact BP trajectories among normotensive pregnancies and have a long-term effect on postpartum weight retention. Thus, reducing PFAS exposure may contribute to improving cardiovascular health for pregnant individuals and their offspring
TOWARD ELECTRICAL IMPEDANCE SENSING SURGICAL DRILL FOR TISSUE BOUNDARY DETECTION
No full textDental implantation is an increasingly common procedure used to treat missing teeth. However, surgical drilling to place the implant poses a high risk of injury to critical anatomy, such as inferior alveolar nerve injury or maxillary sinus perforation. A real-time surgical feedback system sensing proximity of these critical anatomy could reduce injury risks. This dissertation investigates the development of such a system that incorporates an electrical impedance sensor into the tip of a surgical drill.
A simulation framework based on finite element method (FEM) was developed to optimize the sensor as it approached a high impedance boundary. The accuracy of the FEM framework was improved through use of a novel empirical contact impedance model with adaptive mesh refinement strategies. The FEM model closely matched benchtop measurements with an overall mean relative error of +1.7%. Using the simulation platform, the optimal sensing geometry for a 2mm diameter dental-drill was determined to include a 1.6mm exposed length at the drill bit tip.
An in-vivo animal study protocol was developed and followed using 14 adult pigs. 146 holes were drilled, and local impedance data was intermittently recorded at 6 locations on average for each hole. Using intraoperative optical 3D tracking, impedance measurements were located in CT and micro-CT scans. Bone densities were estimated from these scans and compared to impedance measurements.
The cortical boundary thickness when approaching the mandibular canal was 1.29±0.31mm, and when approaching the maxillary sinus was 1.41±0.35 mm. Phase (251 Hz) showed a weak correlation of r = 0.27 with bone density. In homogeneous regions, the correlation with phase (158Hz) improved to r = 0.34. Measuring phase at 251Hz while drilling showed significant differences (p\u3c0.05) between the boundary and layer before boundary, and an area under curve (AUC) of 0.71 was determined to detect critical anatomy. Although these results show smaller differences between tissue type and a smaller ability to detect critical anatomy than expected, this work achieved moderate success (results noted above) and uncovered multiple data-collection challenges that may improve performance in subsequent studies
Methods, Analyses, and Applications of Multilayer Temporal Link Prediction in Networks
Get PDFMany applications stem from the possibility of accurately predicting links in various types of networks. In this thesis, we present methods, analyses, and applications for static, temporal, and multilayer networks. The first part of this thesis demonstrates how static network features serve as efficient and accurate predictors for link prediction in temporal networks. It includes an ensemble learning method we developed and presents experimental results on 90 synthetic stochastic block models and 19 real-world datasets. The second part closely follows, showcasing 20 different sampling methods and their effects on nine different link prediction algorithms for 250 real-world networks across 6 different domains. The third part of this thesis focuses on the analysis of hypergraph modeling and inference for parameters, emphasizing their significance in hypergraph link prediction. Results are demonstrated for 27 real-world hypergraphs of various sizes, some of which contain up to millions of nodes and edges. The last part of this thesis summarizes two applications of link prediction: one in cancer networks and the other in social networks. These applications demonstrate the broad versatility of link prediction algorithms
Microscopic Analysis of Ancient Food Residues
No full textDuring the Longshan period of Neolithic China (c. 3000-2000 BCE), settlements took root and flourished in the Yellow River Valley. Kangjia is an example of such a settlement, with its craft specialization and hierarchical social structure. Furthermore, agriculture and animal husbandry contributed to a relatively varied diet, particularly among those of higher social status.
The primary objective of this experiment was to characterize the diet of Kangjia society. This was accomplished by analyzing plant microfossils sampled from pottery sherds excavated from an archaeological site in Kangjia. Phytoliths, silica plant cell skeletons, have distinct structures which differ between plant species. Similarly, starch granules have characteristic morphological differences between crop species. Because both phytoliths and starch granules are persistent over time, they are ideal diagnostic tools.https://digitalcommons.dartmouth.edu/wetterhahn_2024/1015/thumbnail.jp
Wee1 and Cell Size Control in Fission Yeast by the Protein Kinase Cdr2
Get PDFThe mechanisms that govern cell size have long been topics of study in the field of cell biology. In eukaryotic cells this size control is tied to checkpoints, a set threshold of minimum necessary growth linked to cyclin dependent kinase activity regulation. In the fission yeast Schizosaccharomyces pombe, the Cdk1 regulatory network is conserved, and G2/M represents the major size checkpoint. Prior to mitosis, Cdk1 is inhibited by phosphorylation applied by Wee1 during G2 phase. Once S. pombe cells have satisfied the size checkpoint, Cdk1 is activated through dephosphorylation by Cdc25. Wee1 is a dose-dependent regulator of mitotic entry such that reduction in Wee1 activity results in cells entering mitosis early at small sizes, while increased Wee1 activity causes cells to enter mitosis late at elongated sizes. Control of Wee1 activity is mediated during G2 by the SAD kinases Cdr1 and Cdr2. These kinases coordinate Wee1 inhibition and localize to plasma membrane-associated clusters termed “nodes.” Cdr2 is required to form nodes and its activity is important for retaining Wee1 at a node. Our working model posits that longer retention time of Wee1 at a node allows Cdr1 to inhibit Wee1 catalytic activity through a defined molecular mechanism. Work in this thesis shows development of a new PTet-cdr2 overexpression system that we have validated for Wee1 phenotypes and are using to elucidate the molecular mechanism for Cdr2 regulation of Wee1. We used this system to establish that Cdr2 is a dose-dependent inhibitor of Wee1 through sequestration outside the nucleus. Further, we showed that this inhibition depends on Cdr2 activity and clustering ability. From there, we screened Wee1 for regions likely being phosphorylated by Cdr2 in this mechanism. We have determined that clusters of serine residues in the first 150 amino acids of Wee1 contain the Cdr2-sensitive sites. These findings help to define the mechanism of Wee1 inhibition by Cdr2, where retention at a node dilutes Wee1 away from its substrate Cdk1 in the nucleus. This spatial mechanism works in tandem with Cdr1-based catalytic inhibition to promote mitotic entry at the proper cell size
Gaze in Context: Individual and Group Differences in Real-World Visual Attention
Get PDFWhen exploring a real-world scene, individuals direct their gaze to selectively attend, leaving a trace of their informational priorities. What drives this information selection, and what causes individuals to prioritize information differently from one another? In this dissertation, I aim to understand the influences that guide visual attention as individuals explore real-world environments and to characterize patterns of visual attention that differ among individuals and among groups with neurodevelopmental conditions. In Chapter 1, I introduce a novel eyetracking paradigm, in which participants can actively explore immersive, naturalistic scene photospheres via headmounted virtual reality. Using this paradigm, I demonstrate that naturalistic visual attention is information seeking: when compared to passively seated viewers, active viewers are disproportionately guided by meaningful semantic information. In Chapter 2, I extend this finding by demonstrating that visual attention is a proactive information seeking process guided by individually specific conceptual priorities beyond the visual domain. To show this, I present a new approach for characterizing abstract, conceptual-level information in real-world scenes that draws on recent advancements in natural language modeling. First, in a large cohort of neurotypical adults, I observe “gaze fingerprints”: reliable, individuating patterns of visual attention that generalize across diverse visual stimuli. I then show that conceptual priorities also guide visual attention patterns among autistic adults, and that conceptual gaze models contain classifiable information about a viewer’s diagnostic status. Finally, in Chapter 3, I focus on a specific domain of conceptual information, social information, and investigate how social attention is impacted by the perceptual load of real-world environments among autistic and non-autistic adults. I find that group-level differences are magnified in conditions with higher perceptual load, suggesting that social attention differences are not a static signature of the autistic group. Taken together, the studies I present in my dissertation demonstrate that by studying visual attention under experimental conditions that more closely approximate the conditions of real-world viewing, gaze behavior can offer rich insights, revealing complex signatures of individual minds
“Salmon don’t have time for us to fix the climate”: The politics of climate change and dam breaching on the Lower Snake River
Get PDFThis thesis examines the politics of climate change and dam breach on the Lower Snake River. Located in Southeastern Washington within the Columbia River Basin, the four Lower Snake River dams (LSRD) have long been a source of political and legal controversy. While dam proponents advocate for services that they provide, which includes hydropower, navigation, and irrigation, others contend that their environmental impacts, particularly on salmon and steelhead, make them legally, environmentally, and morally irresponsible. Within this space, I specifically investigate how climate change has influenced the environmental politics and conflicts that surrounds dam breaching, further exploring how competing values and power dynamics shape governance and regulatory practices. Utilizing qualitative methodologies rooted in human geography, I conducted semi-structured interviews with 30 stakeholders, including environmental organizations, industry leaders, and representatives from state and Tribal governments, effectively capturing a range of perspectives on the LSRD conflict. Drawing on concepts from political ecology, science and technology studies, and knowledge controversies, this thesis’ focus on climate change adds to existing scholarship on the politics of dam removal, offering insights into the complex interplay of science and politics that drive contested dam removal efforts. Key findings indicate that while there is consensus on the urgent need for climate action, pre-existing perspectives lead to significant disagreement on whether dam breaching is a necessary and effective solution for climate resilience. This research also reveals the role of climate change within the cross-scalar institutional processes that define policy-making processes for federally owned and operated dams