COMMON: Order Book with Privacy

Decentralized Finance (DeFi) has witnessed remarkable growth and innovation, with Decentralized Exchanges (DEXes) playing a pivotal role in shaping this ecosystem. As numerous DEX designs emerge, challenges such as price inefficiency and lack of user privacy continue to prevail. This paper introduces a novel DEX design, termed COMMON, that addresses these two predominant challenges. COMMON operates as an order book, natively integrated with a shielded token pool, thus providing anonymity to its users. Through the integration of zk-SNARKs, order batching, and Multiparty Computation (MPC) COMMON allows to conceal also the values in orders. This feature, paired with users never leaving the shielded pool when utilizing COMMON, provides a high level of privacy. To enhance price efficiency, we introduce a two-stage order matching process: initially, orders are internally matched, followed by an open, permissionless Dutch Auction to present the assets to Market Makers. This design effectively enables aggregating multiple sources of liquidity as well as helps reducing the adverse effects of Maximal Extractable Value (MEV), by redirecting most of the MEV profits back to the users

Acute Effects of Different Blood Flow Restriction Protocols on Bar Velocity During the Squat Exercise

The main goal of the present study was to evaluate the effects of different blood flow restriction (BFR) protocols (continuous and intermittent) on peak bar velocity (PV) and mean bar velocity (MV) during the squat exercise at progressive loads, from 40 to 90% 1RM. Eleven healthy men (age = 23.4 ± 3.1 years; body mass = 88.5 ± 12.1 kg; squat 1RM = 183.2 ± 30.7 kg; resistance training experience, 5.7 ± 3.6 years) performed experimental sessions once a week for 3 weeks in random and counterbalanced order: without BFR (NO-BFR), with intermittent BFR (I-BFR), and with continuous BFR (C-BFR). During the experimental session, the participants performed six sets of the barbell squat exercise with loads from 40 to 90% 1RM. In each set, they performed two repetitions. During the C-BFR session, the cuffs were maintained throughout the training session. During the I-BFR, the cuffs were used only during the exercise and released for each rest interval. The BFR pressure was set to ∼80% arterial occlusion pressure (AOP). Analyses of variance showed a statistically significant interaction for MV (p < 0.02; η2 = 0.18). However, the post hoc analysis did not show significant differences between particular conditions for particular loads. There was no significant condition × load interaction for PV (p = 0.16; η2 = 0.13). Furthermore, there were no main effects for conditions in MV (p = 0.38; η2 = 0.09) as well as in PV (p = 0.94; η2 = 0.01). The results indicate that the different BFR protocols used during lower body resistance exercises did not reduce peak bar velocity and mean bar velocity during the squat exercise performed with various loads

The tetanic depression in fast motor units of mammalian skeletal muscle can be evoked by lengthening of one initial interpulse interval

A lower than expected tetanic force (the tetanic depression) is regularly observed in fast motor units (MUs) when a higher stimulation frequency immediately follows a lower one. The aim of the present study was to determine whether prolongation of only the first interpulse interval (IPI) resulted in tetanic depression. The experiments were carried out on fast MUs of the medial gastrocnemius muscle in cats and rats. The tetanic depression was measured in each case as the force decrease of a tetanus with one IPI prolonged in relation to the tetanic force at the respective constant stimulation frequency. Force depression was observed in all cases studied and was considerably greater in cats. For cats, the mean values of force depression amounted to 28.64% for FR and 10.86% for FF MUs whereas for rats 9.30 and 7.21% for FR and FF motor units, respectively. Since the phenomenon of tetanic depression in mammalian muscle is commonly observed even after a change in only the initial interpulse interval within a stimulation pattern, it can effectively influence processes of force regulation during voluntary activity of a muscle, when motoneurones progressively increase the firing rate

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Protein Expression Redirects Vesicular Stomatitis Virus RNA Synthesis to Cytoplasmic Inclusions

Positive-strand and double-strand RNA viruses typically compartmentalize their replication machinery in infected cells. This is thought to shield viral RNA from detection by innate immune sensors and favor RNA synthesis. The picture for the non-segmented negative-strand (NNS) RNA viruses, however, is less clear. Working with vesicular stomatitis virus (VSV), a prototype of the NNS RNA viruses, we examined the location of the viral replication machinery and RNA synthesis in cells. By short-term labeling of viral RNA with 5′-bromouridine 5′-triphosphate (BrUTP), we demonstrate that primary mRNA synthesis occurs throughout the host cell cytoplasm. Protein synthesis results in the formation of inclusions that contain the viral RNA synthesis machinery and become the predominant sites of mRNA synthesis in the cell. Disruption of the microtubule network by treatment of cells with nocodazole leads to the accumulation of viral mRNA in discrete structures that decorate the surface of the inclusions. By pulse-chase analysis of the mRNA, we find that viral transcripts synthesized at the inclusions are transported away from the inclusions in a microtubule-dependent manner. Metabolic labeling of viral proteins revealed that inhibiting this transport step diminished the rate of translation. Collectively those data suggest that microtubule-dependent transport of viral mRNAs from inclusions facilitates their translation. Our experiments also show that during a VSV infection, protein synthesis is required to redirect viral RNA synthesis to intracytoplasmic inclusions. As viral RNA synthesis is initially unrestricted, we speculate that its subsequent confinement to inclusions might reflect a cellular response to infection

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures