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A new LUCApedia database for data-driven research on early evolutionary history
No full textMotivation: Many topics within the study of the origin and early evolution of life are amenable to computational research strategies. Over a decade ago, the original LUCApedia was developed in order to facilitate such research. Here we describe a massively overhauled LUCApedia database and web server.
Results: The database is composed of 17 different datasets based on previous studies or published hypotheses about the last universal common ancestor and its evolutionary predecessors. Similar to the original LUCApedia database, these datasets are mapped onto a common framework so that they can be corroborated with one another and used to examine continuity across different stages of early evolution.
Availability and implementation: The database can be searched, browsed, and downloaded from the LUCApedia web server, https://lucapedia.org/
Methylene blue protects oligodendroglial cell models of multiple systems atrophy against hydrogen peroxide-mediated oxidative stress
No full textMultiple Systems Atrophy (MSA) is a rare, neurodegenerative disorder associated with impaired alpha (α)-synuclein (α-syn) protein function. α-syn can aggregate within oligodendrocytes, activating oxidative stress pathways and ultimately leading to cell death. Point mutations in the α-syn gene (SNCA) are associated with MSA–A53E and G51D, but cases are mainly idiopathic. Methylene Blue (MB) is an organic dye that has been demonstrated to attenuate oxidative stress in cell models of Parkinson’s and Huntington’s disease. We hypothesized that MB would protect α-syn stably transfected oligodendroglial cell models of MSA against hydrogen peroxide (H2O2)-induced cellular stress. We used four α-syn stably transfected OLN-93 rat oligodendroglial cell lines expressing either an empty plasmid (EP), overexpressed humanized wild-type α-syn (WT-α-syn), or humanized α-syn with either point mutation (A53E-α-syn, G51D-α-syn). Upon 3 h (h) pre-treatment of OLN-93 cells with MB, followed by 1 h or 3 h exposure to H2O2, we report that MB does not enact toxic effects but rather substantially improves cell viability and metabolic capability and lowers H2O2-induced cell death in the OLN-93 MSA cell models. MB also significantly reduced H2O2-induced early (1 h) ROS production in the cytosol and mitochondria and the expression of oxidative stress and modified antioxidant-related proteins, including Nuclear factor erythroid 2-related factor 2 (NRF2), affiliated Kelch-like ECH-associated protein 1 (KEAP1), Heme Oxygenase 1 (HO1), and Adenosine Monophosphate-Activated Protein Kinase (AMPK) after 3 h exposure. Our current data suggest a novel glioprotective role for MB in MSA pathology, specifically against H2O2-mediated oxidative injury, and invite future work to investigate MB glioprotection in other in vivo MSA models
Direct Access to Acylboranes via Formal Condensation of Carboxylic Acids with Ligated Boranes
No full textThe unique synthetic potential of acylboron species has long attracted attention from the synthetic chemistry community, but their broader application has been limited by challenges associated with their preparation. In this work, we report a mechanistically distinct radical-based C(acyl)–B cross-coupling strategy that enables a “formal condensation” between readily available carboxylic acids and easily accessible ligated boranes. The success of this transformation relies on the distinctive use of a phosphonite ligand, which achieves an optimal balance between the stability and reactivity of the borane moiety. This method demonstrates a broad substrate scope with high practical utility, and its strategic value has been further highlighted through diverse downstream derivatizations of the resulting acylborane compounds
Automated Optimization of Parameterized Data-Plane Programs With Parasol
No full textProgrammable data planes allow for sophisticated applications that give operators the power to customize the functionality of their networks. Deploying these applications, however, often requires tedious and burdensome optimization of their layout and design, in which programmers must manually write, compile, and test an implementation, adjust the design, and repeat. In this paper we present Parasol, a framework that allows programmers to define general, parameterized network algorithms and automatically optimize their various parameters. The parameters of a Parasolprogram can represent a wide variety of implementation decisions, and may be optimized for arbitrary, high-level objectives defined by the programmer. Furthermore, optimization may be tailored to particular environments by providing a representative sample of traffic. We show how we implement the Parasolframework, which consists of a sketching language for writing parameterized programs, and a simulation-based optimizer for testing different parameter settings. We evaluate Parasolby implementing a suite of ten data-plane applications, and find that Parasolproduces a solution with comparable performance to hand-optimized P4 code within a two-hour time budget
Review: Anti-Vice Goes Global : Empire of Purity: The History of Americans\u27 Global War on Prostitution
No full textAC replacement: Heat of the moment or cool-headed choice?
No full textThis paper investigates the determinants of households’ central air conditioner (AC) replacements, one of the larger energy using durable goods that households purchase. We do not find evidence that hot weather or high humidity significantly affect AC replacement rates. However, higher electricity prices and bills increase the likelihood of AC replacement. These findings suggest that clear financial motivators like price incentives could be an effective tool in policymakers’ climate change arsenal going forward
MISTRAL: a model for AGN winds from radiatively efficient accretion in cosmological simulations
No full textFeedback from active galactic nuclei (AGNs) is crucial for regulating galaxy evolution. Motivated by observations of broad absorption line winds from rapidly accreting supermassive black holes (SMBHs), we introduce the mistral AGN feedback model, implemented in the arepo code. mistral comes in two versions: continuous radial (mistral-continuous) and stochastic bipolar momentum deposition (mistral-stochastic). Using the framework of the IllustrisTNG simulations, we explore the effect of mistral on BH and galaxy properties, through an idealized Milky Way-mass galaxy and cosmological zoom simulations run down to . Unlike standard thermal AGN feedback prescriptions, mistral generates galaxy-scale winds that mimic outflows driven by BH accretion. mistral-continuous produces short-lived galactic fountains, and is inefficient at regulating the growth of massive galaxies at . In contrast, mistral-stochastic efficiently suppresses star formation in massive galaxies, reproduces the empirical stellar-to-halo mass relation, and yields a consistent trend of BH-stellar mass evolution. By supporting large-scale outflows while simultaneously preventing gas inflows, mistral-stochastic additionally regulates the cold and hot gas fractions at both galaxy and halo scales. mistral-stochastic therefore works self-consistently across the halo mass range explored , without adopting an SMBH-mass-dependent AGN feedback scheme such as the one used in IllustrisTNG. Our model is a promising tool for predicting the impact of AGN winds on galaxy evolution, and interpreting the growing population of high-redshift galaxies and quasars observed by James Webb Space Telescope. This work is part of the ‘Learning the Universe’ collaboration, which aims to infer the physical processes governing the evolution of the Universe
Family Matters: Examining Family Racial Identity Invalidation Among Biracial People
No full textA common racial stressor for Multiracial people is racial identity invalidation: the experience of having one’s racial identity denied by others. This preregistered, exploratory study investigated Biracial people’s experiences of identity invalidation within a family setting. We used a sample of 383 Biracial adults (Mage = 21.3, SD = 5.8; 72.3% female; 25.8% male; 1.9% transgender/gender non-conforming) to examine the frequency of family racial identity invalidation, its associations with family relations and psychosocial well-being, and characteristics of family members who perpetrated invalidation. Nearly half of participants reported racial identity invalidation from at least one family member, and this rate did not differ between Biracial subgroups (Asian-White, Latine-White, Black-White, Black-Minority, Other minority-White). Within the Latine-White subgroup, family invalidation was negatively associated with family relations and psychosocial well-being. Participants across all subgroups reported experiencing invalidation more frequently from extended family members (e.g., grandparents, aunts/uncles, etc.), compared to immediate family members. However, participants reported invalidation from White and racial minority relatives at similar frequencies. These findings emphasize the salience of extended family members in understanding Multiracial people’s experiences of racial identity invalidation. This study also highlights the need for further research on specific Multiracial subgroups, particularly among Latine-White people
Does descriptive representation matter more now than in the past? A reexamination of Black faces in the mirror in a most-racial era
No full textWe reexamine (Tate, Katherine. 2003. Black Faces in the Mirror: African Americans and Their Representatives in the U.S. Congress. Princeton University Press) Black Faces in the Mirror to better understand whether the significance of descriptive representation has changed two decades after her work on this topic. Similar to (Tate, Katherine. 2003. Black Faces in the Mirror: African Americans and Their Representatives in the U.S. Congress. Princeton University Press), we explore whether descriptive representation continues to be linked to substantive representation and whether this relationship has strengthened or weakened over the past quarter century. To assess this relationship, we examine whether Black Members of Congress in the 104th (1995-1996) and 116th (2019-2020) congressional sessions introduce more Black-oriented legislation. Our results demonstrate that not only do Black legislators consistently provide greater levels of co-racial legislative representation than others, but that this racial gap in substantive representation between Black and non-Black members of Congress has grown over time. Our reexamination of Tate’s work demonstrates that the significance of descriptive representation for underrepresented groups is dynamic and responds to changing racial and political contexts
Accessing \u3ci\u3eN\u3c/i\u3e-Unprotected Unnatural α-Amino Acid Esters by Half-Sandwich Chiral-at-Ruthenium Aldehyde Catalysis: Scope and Mechanistic Study
No full textChiral aldehyde catalysis has emerged as an efficient and step-economical protocol for constructing unnatural α-amino acids and related esters. Herein, we report the application of a half-sandwich chiral-at-ruthenium complex featuring an aldehyde group as a versatile asymmetric catalyst with remarkably broad scope. Direct asymmetric α-C─H functionalization of N-unprotected glycine esters with four types of electrophiles (51 examples, all \u3e91% ee) has been successfully realized for accessing structurally diverse unnatural α-amino acid esters. Gram-scale synthesis and successful catalyst recovery underscored the practicability and application potential of the present asymmetric aldehyde catalysis