Low dilatation pseudo-anosovs on punctured surfaces and volume

For a pseudo-Anosov homeomorphism f on a closed surface of genus g greater of equals to 2, for which the entropy is on the order 1/g (the lowest possible order), Farb-Leininger-Margalit showed that the volume of the mapping torus is bounded, independent of g. We show that the analogous result fails for a surface of fixed genus g with n punctures, by constructing pseudo-Anosov homeomorphism with entropy of the minimal order (log n)/n, and volume tending to infinity

Towards Understanding and Characterizing the Arbitrage Bot Scam In the Wild

This paper presents the first comprehensive analysis of an emerging cryptocurrency scam named "arbitrage bot" disseminated on online social networks. The scam revolves around Decentralized Exchanges (DEX) arbitrage and aims to lure victims into executing a so-called "bot contract" to steal funds from them. To collect the scam at a large scale, we developed a fully automated scam detection system named CryptoScamHunter, which continuously collects YouTube videos and automatically detects scams. Meanwhile, CryptoScamHunter can download the source code of the bot contract from the provided links and extract the associated scam cryptocurrency address. Through deploying CryptoScamHunter from Jun. 2022 to Jun. 2023, we have detected 10,442 arbitrage bot scam videos published from thousands of YouTube accounts. Our analysis reveals that different strategies have been utilized in spreading the scam, including crafting popular accounts, registering spam accounts, and using obfuscation tricks to hide the real scam address in the bot contracts. Moreover, from the scam videos we have collected over 800 malicious bot contracts with source code and extracted 354 scam addresses. By further expanding the scam addresses with a similar contract matching technique, we have obtained a total of 1,697 scam addresses. Through tracing the transactions of all scam addresses on the Ethereum mainnet and Binance Smart Chain, we reveal that over 25,000 victims have fallen prey to this scam, resulting in a financial loss of up to 15 million USD. Overall, our work sheds light on the dissemination tactics and censorship evasion strategies adopted in the arbitrage bot scam, as well as on the scale and impact of such a scam on online social networks and blockchain platforms, emphasizing the urgent need for effective detection and prevention mechanisms against such fraudulent activity.Comment: Accepted by ACM SIGMETRICS 202

Missense VKOR mutants exhibit severe warfarin resistance but lack VKCFD via shifting to an aberrantly reduced state

Missense vitamin K epoxide reductase (VKOR) mutations in patients cause resistance to warfarin treatment but not abnormal bleeding due to defective VKOR activity. The underlying mechanism of these phenotypes remains unknown. Here we show that the redox state of these mutants is essential to their activity and warfarin resistance. Using a mass spectrometry-based footprinting method, we found that severe warfarin-resistant mutations change the VKOR active site to an aberrantly reduced state in cells. Molecular dynamics simulation based on our recent crystal structures of VKOR reveals that these mutations induce an artificial opening of the protein conformation that increases access of small molecules, enabling them to reduce the active site and generating constitutive activity uninhibited by warfarin. Increased activity also compensates for the weakened substrate binding caused by these mutations, thereby maintaining normal VKOR function. The uninhibited nature of severe resistance mutations suggests that patients showing signs of such mutations should be treated by alternative anticoagulation strategies

Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer

The intramembrane vitamin K epoxide reductase (VKOR) supports blood coagulation in humans and is the target of the anticoagulant warfarin. VKOR and its homologs generate disulfide bonds in organisms ranging from bacteria to humans. Here, to better understand the mechanism of VKOR catalysis, we report two crystal structures of a bacterial VKOR captured in different reaction states. These structures reveal a short helix at the hydrophobic active site of VKOR that alters between wound and unwound conformations. Motions of this “horizontal helix” promote electron transfer by regulating the positions of two cysteines in an adjacent loop. Winding of the helix separates these “loop cysteines” to prevent backward electron flow. Despite these motions, hydrophobicity at the active site is maintained to facilitate VKOR catalysis. Biochemical experiments suggest that several warfarin-resistant mutations act by changing the conformation of the horizontal helix. Taken together, these studies provide a comprehensive understanding of VKOR function

Association between red blood cell distribution width and all-cause mortality in unselected critically ill patients: Analysis of the MIMIC-III database

BackgroundAlthough red cell distribution width (RDW) is widely observed in clinical practice, only a few studies have looked at all-cause mortality in unselected critically ill patients, and there are even fewer studies on long-term mortality. The goal of our study was to explore the prediction and inference of mortality in unselected critically ill patients by assessing RDW levels.MethodsWe obtained demographic information, laboratory results, prevalence data, and vital signs from the unselected critically ill patients using the publicly available MIMIC-III database. We then used this information to analyze the association between baseline RDW levels and unselected critically ill patients using Cox proportional risk analysis, smoothed curve fitting, subgroup analysis, and Kaplan–Meier survival curves for short, intermediate, and long-term all-cause mortality in unselected critically ill patients.ResultsA total of 26,818 patients were included in our study for the final data analysis after screening in accordance with acceptable conditions. Our study investigated the relationship between RDW levels and all-cause mortality in a non-selected population by a smoothed curve fit plots and COX proportional risk regression models integrating cubic spline functions reported results about a non-linear relationship. In the fully adjusted model, we found that RDW values were positively associated with 30-day, 90-day, 365-day, and 4-year all-cause mortality in 26,818 non-selected adult patients with HRs of 1.10 95%CIs (1.08, 1.12); 1.11 95%CIs (1.10, 1.13); 1.13 95%CIs (1.12, 1.14); 1.13 95%CIs (1.12, 1.14).ConclusionIn unselected critically ill patients, RDW levels were positively associated with all-cause mortality, with elevated RDW levels increasing all-cause mortality

Termini restraining of small membrane proteins enables structure determination at near-atomic resolution

Small membrane proteins are difficult targets for structural characterization. Here, we stabilize their folding by restraining their amino and carboxyl termini with associable protein entities, exemplified by the two halves of a superfolder GFP. The termini-restrained proteins are functional and show improved stability during overexpression and purification. The reassembled GFP provides a versatile scaffold for membrane protein crystallization, enables diffraction to atomic resolution, and facilitates crystal identification, phase determination, and density modification. This strategy gives rise to 14 new structures of five vertebrate proteins from distinct functional families, bringing a substantial expansion to the structural database of small membrane proteins. Moreover, a high-resolution structure of bacterial DsbB reveals that this thiol oxidoreductase is activated through a catalytic triad, similar to cysteine proteases. Overall, termini restraining proves exceptionally effective for stabilization and structure determination of small membrane proteins

Minimally Invasive Delivery of 3D Shape Recoverable Constructs with Ordered Structures for Tissue Repair

Minimally invasive procedures are becoming increasingly more common in surgery. However, the biomaterials capable of delivering biomimetic, three-dimensional (3D) functional tissues in a minimally invasive manner and exhibiting ordered structures after delivery are lacking. Herein, we reported the fabrication of gelatin methacryloyl (GelMA)-coated, 3D expanded nanofiber scaffolds and their potential applications in minimally invasive delivery of 3D functional tissue constructs with ordered structures and clinically appropriate sizes (4 cm × 2 cm × 1.5 mm). GelMA-coated, expanded 3D nanofiber scaffolds produced by combining electrospinning, gas-foaming expansion, hydrogel coating, and crosslinking are extremely shape recoverable after release of compressive strain, displaying a superelastic property. Such scaffolds can be seeded with various types of cells, including dermal fibroblasts, bone marrow-derived mesenchymal stem cells, and human neural stem/precursor cells to form 3D complex tissue constructs. Importantly, the developed 3D tissue constructs can be compressed and loaded into a 4-mm diameter glass tube for minimally invasive delivery without compromising the cell viability. Taken together, the method developed in this study could hold great promise for transplantation of biomimetic, 3D functional tissue constructs with well-organized structures for tissue repair and regeneration using minimally invasive procedures like laparoscopy and thoracoscopy