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Breaking: DDC Enjoins Part of Trump Elections Executive Order
No full textThe preliminary injunction in LULAC v. Executive Office of the President was issued by Judge Kollar-Kotelly of the U.S. District Court for the District of Columbia (DDC). The proceedings involve three consolidated cases: two brought by civil rights groups and one brought by the Democratic Party. The parties sought preliminary injunctions against five provisions of the EO. The DDC enjoined only two provisions: Sections 2(a) and 2(d)
Electrochemical Hydrogen Pump – Methods to Combat CO Poisoning
Full text linkAs global demand for hydrogen grows, both as a clean energy carrier and an industrial fuel, electrochemical hydrogen pumps (EHPs) are gaining attention for their ability to separate and compress hydrogen efficiently. EHPs work by selectively drawing hydrogen from low-pressure hydrogen gas mixtures and electrochemically converting it into high-purity, high-pressure hydrogen. EHPs are particularly useful for purifying hydrogen from industrial byproducts like syngas, an industrial mixture containing hydrogen and carbon monoxide (CO). However, CO binds to the platinum catalyst used in EHPs and reduces its effectiveness – a problem known as catalyst poisoning.
This literature review explores a range of strategies being developed to address CO poisoning in EHPs, including catalyst modifications (such as platinum alloys and platinum group metal-free alternatives), membrane material innovations (e.g., ion exchange vs. proton exchange membranes), and operational methods like high-temperature systems and pulsing techniques. Pulsing strategies involve either modulating the applied current or using oxygen bleeds to regenerate poisoned catalysts. These approaches are compared based on key performance metrics such as hydrogen output, faradaic efficiency, and long-term stability. The paper also discusses where each method works best, their trade-offs, and provides a clearer picture of how to build more CO-tolerant and efficient EHP systems
SPINOR: Exploring the sub-30 MHz Radio Sky in Fine Resolution for the First Time
Full text linkThe SPINOR (Spinning Past-Ionospheric Network for Observation of Radio) program is developing tunable, narrow-band, resonant antenna networks for observing radio frequencies below 30 MHz. This frequency range has not been studied since exploratory missions in the 1960s due to ionospheric blockage requiring large space-based missions, but it offers unprecedented scientific observations. These include capturing direct observations of exoplanet magnetospheres and their interactions with solar magnetic fields, advancing heliophysics and space weather monitoring, exploring solar system magnetospheres and lightning, and mapping the redshifted 21 cm hydrogen line from the early universe.
Most existing proposals to fill this observational gap employ large constellations of satellites for interferometry due to the long wavelengths. For example, GO-LoW is an MIT Haystack Observatory proposal for an interferometric mega constellation of 3U CubeSats with vector sensors. Its electrically short sensors enable simultaneous full-sky fine spatial and spectral resolution mapping, but their low sensitivity requires a very large constellation size to observe faint sources.
SPINOR consists of spinning, deployable tethers with adjustable lengths to produce high-sensitivity maps across multiple resonant frequencies. This approach enables groundbreaking observations with a smaller constellation size compared to traditional interferometric designs. By leveraging modern super-resolution algorithms and a stable rotating beam pattern, SPINOR offers repeated all-sky coverage and unbiased surveys of the radio sky.
Several technologies require demonstration, including low-noise readout electronics, tether deployment, precise attitude determination during slew, and deconvolution algorithms. High-altitude balloons, sounding rockets, and LEO, GTO, and cislunar CubeSats will be used to demonstrate this program’s feasibility
A Role for the Actin Cytoskeleton and Plastin-3 in Osteoblast Mineralization and Mechanosensation
Full text linkThe great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes including cell migration, intracellular trafficking, and cell division. One such system that relies on the actin cytoskeleton to fulfill its physiological function are osteoblasts, which are mesenchymal lineage bone cells that promote bone formation through depositing a collagen scaffold and subsequently promoting mineralization of this matrix. A number of factors are known to drive osteogenic differentiation of pre-osteoblast cells including extracellular matrix cues such as substrate stiffness, which are primarily detected via mechanosensitive machinery linked to the actin cytoskeleton. Disruptions to β-actin, actin cytoskeletal dynamics, and actin-associated proteins have all been shown to disrupt both osteoblast physiology at the cellular level as well as the integrity of bone structure in model systems. This emphasizes that careful tuning of actin filament dynamics is required for osteoblast differentiation and function, which thus raises the question of how actin-binding proteins contribute to these processes. In this work, we take two approaches to explore the significance of regulatory mechanisms governing actin cytoskeleton dynamics. In the first part of this work, we directly compare how processing and modification of the N terminus of β-actin affects intrinsic polymerization dynamics and its remodeling by actin-binding proteins that are essential for cell migration. In the second part of this work, we investigate the role of plastin-3 (PLS3) in osteoblast physiology. PLS3 is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis, however, the underlying mechanism remains elusive. To investigate the role of PLS3 in osteoblasts, we generated MC3T3-E1 pre- osteoblast cells that are stably depleted of PLS3. Comparison of osteogenic differentiation in control and PLS3 knockdown cells reveals that depletion of PLS3 does not alter the first stage of osteoblast differentiation in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. Osteogenic differentiation heavily relies on mechanosensitive pathways including those linked to focal adhesions to drive mineral deposition. We observed PLS3 prominently localizes to focal adhesions (FAs) and that depletion of PLS3 rendered osteoblasts unresponsive to changes in ECM stiffness. More specifically, our results reveal pre-osteoblasts depleted of PLS3 exhibit similar cell sizes, FA lengths, and number of FAs when plated on soft (6 kPa) versus stiff (100 kPa) substrates in contrast to control cells, which showed an increased in each of these parameters when plated on 100 kPa substrates. Defective cell spreading of PLS3 KD cells on stiff substrates could be rescued by expression of wildtype PLS3, but not by expression of three PLS3 mutants that were identified in patients with early-onset osteoporosis and that have aberrant actin-bundling activity. Altogether, our results show that actin-bundling by PLS3 is part of the mechanosensitive mechanism that promotes osteoblast mineralization and thus begins to elucidate how PLS3 contributes to the development of bone defects such as osteoporosis
Computational Methods and Optimization for Naturalistic Functional Brain Mapping Using Diffuse Optical Tomography
No full textNaturalistic neuroimaging has significantly advanced our understanding of the brain in everyday situations. Stimulus designs that previously targeted individual brain regions are now being replaced by activities such as watching movies, engaging in conversations, and interacting with virtual reality environments. However, traditional functional neuroimaging techniques like functional magnetic resonance imaging (fMRI) are inherently unnaturalistic, as participants must lay down and remain still within the magnet\u27s bore. Consequently, these naturalistic paradigms require an equally naturalistic neuroimaging modality. High-density diffuse optical tomography (HD-DOT) offers a wearable alternative to fMRI by utilizing overlapping optical measurements to densely sample cortical brain activity. HD-DOT has proven effective in mapping brain responses to features from audiovisual movies, indicating that this method is appropriate for naturalistic neuroimaging. Here, we aim to optimize computational methods to advance naturalistic neuroimaging using HD-DOT. With movie viewing as an accessible naturalistic task, we map (or encode) audiovisual features, including concurrent features such as speech and faces from animated clips. We further demonstrate the feasibility of multi-sensory decoding by predicting which movie clip a participant viewed based on their DOT data. To improve our DOT data, we constructed a very high-density DOT imaging system for whole-head, high-resolution optical neuroimaging. This was validated in healthy adults completing functional localizer and movie-viewing tasks and was directly compared to fMRI. Decoding tasks underscore the repeatability of our signal, which is essential for naturalistic neuroimaging studies. Finally, a simulation approach was introduced to estimate the performance of optical neuroimaging systems using large-scale fMRI datasets. This provides a data-driven method for decision-making regarding new imaging systems and stimulus designs. Overall, this dissertation establishes and optimizes computational methods for naturalistic neuroimaging using DOT as a wearable surrogate for fMRI
Algorithmic Governance and Nondiscrimination Rights in the Workplace
Full text linkThis chapter analyzes existing legal responses to the problem of discriminatory algorithms in the workplace. As firms increasingly rely on algorithms or automated decision systems, a type of artificial intelligence, to manage their workforces, concerns have grown that these tools can systematically exclude historically disadvantaged groups. One response is to rely on traditional anti-discrimination law. These laws clearly prohibit certain forms of algorithmic discrimination; however, the complex, opaque nature of algorithms makes identifying and proving discriminatory harms challenging. Another response looks to broader frameworks of data protection and algorithmic regulation to protect against workplace discrimination. These initiatives are promising, but much depends on their details. Individual data rights are of limited usefulness because of the systemic nature of algorithmic discrimination, while broad regulatory oversight can help improve transparency and oversight of these tools
The Dragon\u27s Eye: A Quest for Tabletop Role-Playing\u27s Visual Culture
No full textThe world of Tabletop Role-Playing Games (TRPGs) has always been defined and dominated by Dungeons & Dragons (D&D), the game that pioneered the industry in the 1970’s. Meanwhile during this time, independent games have consistently innovated new ways of utilizing this highly creative field both in contrast and in concert with D&D’s growth. As a decade-long player and developing creator of these games, I hold a vested interest in furthering our understanding of them. The visual aspects of these products are well-documented and celebrated, but in this essay I attempt to define the overall landscape of TRPG visual culture across its illustrations, graphic design, marketing, and other supplementary multi-media.
This definition is built upon analyzing the underlying motivations behind each game and how this shapes the creative choices made in the visual sphere. I first establish a groundwork understanding of the prototypical structure of all Tabletop RPGs, from which each game uniquely adheres to or departs from. Then, I define Dungeons & Dragons from a historical angle, its visual choices deeply motivated by paying homage to its own history while evolving to suit the changing preferences of its incredibly wide audience. The market of independent and small-publisher games is much more vast and varied, instead being defined by the sheer diversity of approaches taken and new innovations being made.
The sum of these explorations allows for a wider and deeper understanding of the place that visuals serve in the TRPG industry. With this landscape further defined, makers of the field can create with an educated sense of the conventions that they may choose to honor, innovate, or break away from. I also further affirm the crucial motivator that ties together all creative endeavors within this field: community
Leveraging arginine catabolism to treat metabolic complications
No full textFasting and caloric restriction are effective to treat patients with pre-diabetes or metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), but intensive lifestyle changes are difficult for many to implement and sustain. Therefore, by identifying and studying fasting-mediated signals, we hope to elicit and convey the therapeutic effects of fasting against MASLD without actual physiological fasting. We discovered a key pathway in the liver through unbiased transcriptomic screening in fasted mice, a novel glucose fasting-activated effector: the amino acid hydrolase, arginase 2 (ARG2). Our previously published data demonstrates that forced hepatocyte-specific Arg2 overexpression is sufficient to reduce peripheral insulin resistance and hepatic steatosis in pre-diabetic and MASLD models in mice. In this thesis, I am to investigate how ARG2 conveys its therapeutic effects and examine its efficacy to bring forth new therapies that mimic the actions of ARG2 to ultimately treat MASLD and MASLD-related metabolic disease. In the first part of my thesis, I define the structure-function relationship between ARG2 mitochondrial localization, arginine hydrolase activity, and the metabolic effects of ARG2. I generated and tested two ARG2 mutant constructs, one lacking the putative N-terminal mitochondrial targeting sequence (MTS, Arg21-22) and the other lacking its ureahydrolytic activity (Arg2H160F). Hepatocyte-specific overexpression of the mutant constructs in obese, diabetic (db/db) mice showed ARG2 attenuates hepatic steatosis independent of mitochondrial localization or ureahydrolase activity, and that enzymatic activity is dispensable for ARG2 to augment total body energy expenditure. Furthermore, ARG2-mediated increase in glucose-, insulin tolerance, and glucose appearance suppression during hyperinsulinemic-euglycemic clamping requires both mitochondrial localization and ureahydrolase activity. Seahorse respirometry in hepatocytes in vitro, and quantification of heavy-isotope-labeled glucose oxidation in vivo further revealed that both Arg21-22 and Arg2H160F mutants failed to induce ARG2-mediated increase in hepatic and systemic oxidative metabolism, respectively. These results further complement our previous work in ARG2 by providing a structure-based mechanism of ARG2 with respect to its metabolic effects and demonstrating that hepatic Arg2 is a prominent metabolic gene. In the second part of my thesis, I investigate the contribution of and necessity for hepatocyte ARG2 in prevention against MASLD progression to confer the metabolic effects in the pathogenesis of MASLD and its related metabolic complications. The results demonstrate that hepatocyte-specific Arg2 deletion impairs ureagenesis, TCA cycle, and mitochondrial function which has real physiological metabolic consequences. Hepatocyte-specific Arg2-deficiency drives obesity, liver steatosis, and insulin resistance in aging-associated metabolic decline and diet-induced mouse models of MASLD. Mechanistically, impaired oxidative metabolism and MASH in Arg2LKO mice is reversible through supplementation of NAD+ via nicotinamide mononucleotide or nicotinamide riboside. Translationally, Arg2-deficiency generates metabolite alterations in nitrogen flux, TCA cycle flux, and oxidative metabolism which is consistent with biomarkers perturbation that independently predict severe incident MASLD/MASH nearly a decade in advance from 106,606 healthy participants in the UK Biobank. Therefore, hepatocyte-specific Arg2-deficiency represents as a new paradigm to demonstrate the urea cycle’s hierarchical control over TCA cycle flux to regulate mitochondrial oxidative metabolism. Together, providing mechanistic insight into the long-observed association between urea cycle impairment and MASLD. We then identified a readily available pharmacological reagent, ADI-PEG 20, and found arginine depletion via ADI-PEG 20 is viable and holds great therapeutic potential as a candidate for treatment against obesity and MASLD. Furthermore, ADI-PEG 20 treatment induced favorable metabolic effects that were independently abolished in mice with liver-specific Fgf21 and Becn1 deletion. This study reveals a novel role of arginine catabolism in the pathophysiology of MASLD which is dependent on liver-specific functions such as FGF21 and autophagy. Together, our findings suggest that hepatocyte arginine status is central and modifiable in treatments against MASLD and metabolic complications
Experimental Evaluation of Resource Allocation to Organelles in Eukaryotic Cells
Full text linkAmong the hallmarks of the eukaryotic cell is its organization into spatially defined sub-compartments known as organelles. Organelles provide optimized environments for otherwise incompatible biochemical reactions within the cell. It has been shown that there is significant variation in the properties of organelles in a cell, and that cells have access to a limited pool of resources that they can allocate to organelles. This begs the question: by what principles do cells dictate how resources are allocated? To begin to explore this question, we look at resource allocation in S. cerevisiaefrom two perspectives. First, we use a combination of theory and experiment to characterize organelle size-number optimization. Second, we use experiment to study the variation in protein expression in organelles. We propose that cellular resource allocation to organelle number and size is consistent with a simple optimality principle: resources are optimally allocated to organelle number and size growth for de novo synthesized organelles, while organelle numbers and sizes themselves are optimized for fission derived organelles. We also show a quantitative measure of intra-cellular variation in protein expression. This work represents a potential step toward uncovering the general rules that dictate resource allocation decisions during the processes eukaryotic cells use to build their organelles
Puerto Ricans as a Case Study for the Adoption of Gender Inclusive Language in Spanish
Full text linkMy research question is: why do people decide to use or not use gender inclusive language? How might demographics such as age, gender identity, or sexual orientation influence this reasoning? My interviews revealed varying definitions of what gender inclusive language means to speakers, the importance of sociocultural context in its use, and future possibilities for its development as a tool for community building and allyship