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Cross-party violence – violence between opposing partisans – is a growing concern worldwide. Understanding the predictors of the legitimization of violence against political opponents is thus becoming a vital goal. In this work, we propose two potential explanatory frameworks: affective polarization and low non-violent group efficacy. The first reflects an affective motivation to harm the out-party, while the latter reflects an instrumental motivation to deploy violence. Furthermore, while the former is frequently suggested in scholarly work as a cause for such violence, it has so far been backed only by limited empirical support. On the other hand, the latter is hardly examined in the context of interactions between opposing partisans. We tested the relationship of the two explanatory frameworks with the legitimization of cross-party violence using public opinion surveys in two real-world contexts: in 2020, in Israel (N = 500) and in the US (N = 631). Results from a regression analysis provide support for the instrumental explanation but not for the affective one. We discuss the theoretical implications of our findings for the research of affective polarization, and potential practical implications for attempts to reduce cross-party violence.

Binary compositions of surface ligands are known to improve the colloidal stability and fluorescence quantum yield of nanocrystals (NCs), due to ligand-ligand interactions and surface organization. Herein, we follow the thermodynamics of a ligand exchange reaction of CdSe NCs with alkylthiols mixtures. The effects of ligand polarity and length difference on ligand packing were investigated using isothermal titration calorimetry (ITC). The thermodynamic signature of the formation of mixed ligand shells was observed. Correlating the experimental results with thermodynamic mixing models has allowed us to calculate the inter-chain interactions and infer the final ligand shell configuration. Our findings demonstrate that the small dimensions of the NCs and the subsequent increased interfacial region between dissimilar ligands, in contrast to macroscopic surfaces, allow the formation of a myriad of clustering patterns, controlled by the inter-ligand interactions. This work provides a fundamental understanding of the parameters determining the ligand shell structure and should help guide smart surface design toward NC-based applications., 28 pages, 4 figures; combines with SI file 24 pages, 14 figures, 9 tables

Changes in mitochondrial morphology are associated with nutrient utilization, but the precise causalities and the underlying mechanisms remain unknown. Here, using cellular models representing a wide variety of mitochondrial shapes, we show a strong linear correlation between mitochondrial fragmentation and increased fatty acid oxidation (FAO) rates. Forced mitochondrial elongation following MFN2 over-expression or DRP1 depletion diminishes FAO, while forced fragmentation upon knockdown or knockout of MFN2 augments FAO as evident from respirometry and metabolic tracing. Remarkably, the genetic induction of fragmentation phenocopies distinct cell type-specific biologicalfunctions of enhanced FAO. These include stimulation of gluconeogenesis in hepatocytes, induction of insulin secretion in islet β-cells exposed to fatty acids,and survival of FAO-dependent lymphoma subtypes. We find that fragmentation increases long-chain but not short-chain FAO,identifying carnitine O-palmitoyltransferase 1 (CPT1) as thedownstream effector of mitochondrial morphology in regulation of FAO.Mechanistically, we determined that fragmentation reduces malonyl-CoA inhibition of CPT1, while elongation increasesCPT1sensitivity to malonyl-CoA inhibition. Overall, these findings underscore a physiologic role for fragmentation as a mechanism whereby cellular fuel preference and FAO capacity are determined.

The purpose of this study is to be able to find out how the implementation of the BSPS Program affects the handling of RTLH and Extreme Poverty in Kemas Rindo Village, Kertapati District, Palembang City. The data used is secondary data from BKKBN. The data is RTLH data in Palembang City precisely during 2022. Furthermore, the data is analyzed using quantitative descriptive analysis which will later show the distribution of RTLH in the city of Palembang. Other supporting data was obtained based on the Documentation of Kemas Rindo Village Based on the Type and Number of Livelihoods of residents in the Kemas Rindo Village environment, Kertapati District, Palembang City. The results of the discussion that have been presented are related to how the implementation stages of the BSPS Program in Kemas Rindo Village have run well, as evidenced by the development of 53 Habitable Self-Help Housing Units. Then, related to infrastructure, a 917-meter environmental road has also been made for community travel access in Kemas Rindo Village. The completion of RTLH and Extreme Poverty is a manifestation of the Government's concern in alleviating poverty for MBR and it is hoped that this assistance can be felt by all people in need

SUMMARYSARS-CoV-2 can infect cells through endocytic uptake, a process which can be targeted by inhibition of lysosomal proteases. However, clinically this approach fared poorly with an oral regimen of hydroxychloroquine that was accompanied by significant toxicity due to off-target effects. We rationalized that an organelle-targeted approach will avoid toxicity while increasing the concentration of the drug at the target. Here we describe a lysosome-targeted, mefloquine-loaded poly(glycerol monostearate-co-ε-caprolactone) nanoparticle (MFQ-NP) for pulmonary delivery via inhalation. Mefloquine is a more effective inhibitor of viral endocytosis than hydroxychloroquine in cellular models of COVID-19. MFQ-NPs are less toxic than molecular mefloquine, 100-150 nm in diameter, and possess a negative surface charge which facilitates uptake via endocytosis allowing inhibition of lysosomal proteases. MFQ-NPs inhibit coronavirus infection in mouse MHV-A59 and human OC43 coronavirus model systems and inhibit SARS-CoV-2-WA1 and its Omicron variant in a human lung epithelium model. This study demonstrates that organelle-targeted delivery is an effective means to inhibit viral infection.

Sulfoxides and selenoxides oxidize thiols to disulfides while being reduced back to sulfides and selenides. While the reduction mechanism of sulfoxides to sulfides has been thoroughly explored experimentally as well as computationally, less attention has been devoted to the heavier selenoxides. In this work, we explore the reductive mechanism of dimethyl selenoxide, as an archetypal selenoxide and, for the sake of comparison, the reductive mechanism of dimethyl sulfoxide to gain insight into the role of the chalcogen on the reaction substrate. Particular attention is devoted to the key role of sulfurane and selenurane intermediates. Moreover, the capacity of these system to oxidize selenols rather than thiols, leading to the formation of selenyl sulfide bridges, is explored in silico. Notably, this analysis provides molecular insight into the role of selenocysteine in methionine sulfoxide reductase selenoenzyme. The activation strain model of chemical reactivity is employed in the studied reactions as an intuitive tool to bridge the computationally predicted effect of the chalcogen on the chalcogenoxide as well as on the chalcogenol.

Adaptation of the islet β-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β-cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme Lysine-specific demethylase 1 (Lsd1) in islets. β-cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome.

The Discrete Fourier Transform (DFT) is essential for various applications ranging from signal processing to convolution and polynomial multiplication. The groundbreaking Fast Fourier Transform (FFT) algorithm reduces DFT time complexity from the naive O(n^2) to O(n log n), and recent works have sought further acceleration through parallel architectures such as GPUs. Unfortunately, accelerators such as GPUs cannot exploit their full computing capabilities as memory access becomes the bottleneck. Therefore, this paper accelerates the FFT algorithm using digital Processing-in-Memory (PIM) architectures that shift computation into the memory by exploiting physical devices capable of storage and logic (e.g., memristors). We propose an O(log n) in-memory FFT algorithm that can also be performed in parallel across multiple arrays for high-throughput batched execution, supporting both fixed-point and floating-point numbers. Through the convolution theorem, we extend this algorithm to O(log n) polynomial multiplication - a fundamental task for applications such as cryptography. We evaluate FourierPIM on a publicly-available cycle-accurate simulator that verifies both correctness and performance, and demonstrate 5-15x throughput and 4-13x energy improvement over the NVIDIA cuFFT library on state-of-the-art GPUs for FFT and polynomial multiplication.

We argue that museums presenting exhibits of ancient texts may be able to benefit from accompanying them with annotated electronic versions. We present a short study using two sample annotated texts built using the Learning And Reading Assistant (LARA) platform for a fragment of an Old Norse manuscript and an inscription in Ancient Egyptian hieroglyphs respectively. The results of an online questionnaire suggested that people already interested in ancient languages would view the idea very positively.

Funder: UCLA Intercampus Medical Genetics Training Program (T32GM008243), NRSA predoctoral fellowship (F31DK108657), Carl V. Gisolfi Memorial Research grant from the American College of Sports Medicine, and a predoctoral graduate student award from the Dornsife College at the University of Southern California., Funder: EMBO long-term fellowship ALTF 828-2021, Funder: DK120342, DK117850, Funder: DK109724, P30DK063491, Funder: NIDDK DK125354, Parkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control. However, the mechanisms by which Parkin connects mitochondrial homeostasis with cellular metabolism in adipose tissue remain unclear. Here, we demonstrate that Park2 gene (encodes Parkin) deletion specifically from adipose tissue protects mice against high-fat diet and aging-induced obesity. Despite a mild reduction in mitophagy, mitochondrial DNA content and mitochondrial function are increased in Park2 deficient white adipocytes. Moreover, Park2 gene deletion elevates mitochondrial biogenesis by increasing Pgc1α protein stability through mitochondrial superoxide-activated NAD(P)H quinone dehydrogenase 1 (Nqo1). Both in vitro and in vivo studies show that Nqo1 overexpression elevates Pgc1α protein level and mitochondrial DNA content and enhances mitochondrial activity in mouse and human adipocytes. Taken together, our findings indicate that Parkin regulates mitochondrial homeostasis by balancing mitophagy and Pgc1α-mediated mitochondrial biogenesis in white adipocytes, suggesting a potential therapeutic target in adipocytes to combat obesity and obesity-associated disorders.