Numerical Study of Tire Hydroplaning Based on Power Spectrum of Asphalt Pavement and Kinetic Friction Coefficient

Hydroplaning is a driving phenomenon threating vehicle’s control stability and safety. It happens when tire rolls on wet pavement with high speed that hydrodynamic force uplifts the tire. Accurate numerical simulation to reveal the mechanism of hydroplaning and evaluate the function of relevant factors in this process is significant. In order to describe the friction behaviors of tire-pavement interaction, kinetic friction coefficient curve of tire rubber and asphalt pavement was obtained by combining pavement surface power spectrum and complex modulus of tread rubber through Persson’s friction theory. Finite element model of tire-fluid-pavement was established in ABAQUS, which was composed of a 225-40-R18 radial tire and three types of asphalt pavement covered with water film. Mechanical responses and physical behaviors of tire-pavement interaction were observed and compared with NASA equation to validate the applicability and accuracy of this model. Then contact force at tire-pavement interface and critical hydroplaning speed influenced by tire inflation pressure, water film thickness, and pavement types were investigated. The results show higher tire inflation pressure, thinner water film, and more abundant macrotexture enhancing hydroplaning speed. The results could be applied to predict hydroplaning speed on different asphalt pavement and improve pavement skid resistance design

Q-Diffusion: Quantizing Diffusion Models

Diffusion models have achieved great success in image synthesis through iterative noise estimation using deep neural networks. However, the slow inference, high memory consumption, and computation intensity of the noise estimation model hinder the efficient adoption of diffusion models. Although post-training quantization (PTQ) is considered a go-to compression method for other tasks, it does not work out-of-the-box on diffusion models. We propose a novel PTQ method specifically tailored towards the unique multi-timestep pipeline and model architecture of the diffusion models, which compresses the noise estimation network to accelerate the generation process. We identify the key difficulty of diffusion model quantization as the changing output distributions of noise estimation networks over multiple time steps and the bimodal activation distribution of the shortcut layers within the noise estimation network. We tackle these challenges with timestep-aware calibration and split shortcut quantization in this work. Experimental results show that our proposed method is able to quantize full-precision unconditional diffusion models into 4-bit while maintaining comparable performance (small FID change of at most 2.34 compared to >100 for traditional PTQ) in a training-free manner. Our approach can also be applied to text-guided image generation, where we can run stable diffusion in 4-bit weights with high generation quality for the first time.Comment: The code is available at https://github.com/Xiuyu-Li/q-diffusio

TorchSparse++: Efficient Training and Inference Framework for Sparse Convolution on GPUs

Sparse convolution plays a pivotal role in emerging workloads, including point cloud processing in AR/VR, autonomous driving, and graph understanding in recommendation systems. Since the computation pattern is sparse and irregular, specialized high-performance kernels are required. Existing GPU libraries offer two dataflow types for sparse convolution. The gather-GEMM-scatter dataflow is easy to implement but not optimal in performance, while the dataflows with overlapped computation and memory access (e.g.implicit GEMM) are highly performant but have very high engineering costs. In this paper, we introduce TorchSparse++, a new GPU library that achieves the best of both worlds. We create a highly efficient Sparse Kernel Generator that generates performant sparse convolution kernels at less than one-tenth of the engineering cost of the current state-of-the-art system. On top of this, we design the Sparse Autotuner, which extends the design space of existing sparse convolution libraries and searches for the best dataflow configurations for training and inference workloads. Consequently, TorchSparse++ achieves 2.9x, 3.3x, 2.2x and 1.7x measured end-to-end speedup on an NVIDIA A100 GPU over state-of-the-art MinkowskiEngine, SpConv 1.2, TorchSparse and SpConv v2 in inference; and is 1.2-1.3x faster than SpConv v2 in mixed precision training across seven representative autonomous driving benchmarks. It also seamlessly supports graph convolutions, achieving 2.6-7.6x faster inference speed compared with state-of-the-art graph deep learning libraries.Comment: MICRO 2023; Haotian Tang and Shang Yang contributed equally to this projec

Pathogenic Mutations Differentially Regulate Cell-to-Cell Transmission of α-Synuclein

Recent studies suggest that the cell-to-cell spread of pathological α-synuclein (α-syn) plays important roles in the development of Parkinson’s disease (PD). PD patients who carry α-syn gene mutations often have an earlier onset and more severe clinical symptoms and pathology than sporadic PD cases who carry the wild-type (WT) α-syn gene. However, the molecular mechanism by which α-syn gene mutations promote PD remains unclear. Here, we hypothesized that pathogenic mutations facilitate the intercellular transfer and cytotoxicity of α-syn, favoring an early disease onset and faster progression. We investigated the effects of eight known pathogenic mutations in human α-syn (A18T, A29S, A30P, E46K, H50Q, G51D, A53E, and A53T) on its pathological transmission in terms of secretion, aggregation, intracellular level, cytotoxicity, seeding, and induction of neuroinflammation in SH-SY5Y neuroblastoma cells, cultured rat neurons, and microglia, and the rat substantia nigra pars compacta. We found that 2 of the 8 mutations (H50Q and A53T) significantly increased α-syn secretion while 6 mutations (A18T, A29S, A30P, G51D, A53E, and E46K) tended to enhance it. In vitroα-syn aggregation experiments showed that H50Q promoted while G51D delayed aggregation most strongly. Interestingly, 3 mutations (E46K, H50Q, and G51D) greatly increased the intracellular α-syn level when cultured cells were treated with preformed α-syn fibrils (PFFs) compared with the WT, while the other 5 had no effect. We also demonstrated that H50Q, G51D, and A53T PFFs, but not E46K PFFs, efficiently seeded in vivo and acutely induced neuroinflammation in rat substantia nigra pars compacta. Our data indicate that pathogenic mutations augment the prion-like spread of α-syn at different steps and blockade of this pathogenic propagation may serve as a promising therapeutic intervention for PD

Comparison of Diagnostic Performance of Three-Dimensional Positron Emission Mammography versus Whole Body Positron Emission Tomography in Breast Cancer

Objective. To compare the diagnostic performance of three-dimensional (3D) positron emission mammography (PEM) versus whole body positron emission tomography (WBPET) for breast cancer. Methods. A total of 410 women with normal breast or benign or highly suspicious malignant tumors were randomized at 1 : 1 ratio to undergo 3D-PEM followed by WBPET or WBPET followed by 3D-PEM. Lumpectomy or mastectomy was performed on eligible participants after the scanning. Results. The sensitivity and specificity of 3D-PEM were 92.8% and 54.5%, respectively. WBPET showed a sensitivity of 95.7% and specificity of 56.8%. After exclusion of the patients with lesions beyond the detecting range of the 3D-PEM instrument, 3D-PEM showed higher sensitivity than WBPET (97.0% versus 95.5%, P = 0.913), particularly for small lesions (<1 cm) (72.0% versus 60.0%, P = 0.685). Conclusions. The 3D-PEM appears more sensitive to small lesions than WBPET but may fail to detect lesions that are beyond the detecting range. This study was approved by the Ethics Committee (E2012052) at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The instrument positron emission mammography (PEMi) was approved by China State Food and Drug Administration under the registration number 20153331166

Safety and efficacy of plasma exchange treatment in children with AQP4-IgG positive neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD), a severe demyelinating disease, is rare among children. Plasma exchange (PE) is widely used as a salvage therapy for severe and corticosteroid-unresponsive patients with NMOSD. Presently, there are limited studies on the safety and efficacy of PE in children with NMOSD. Herein, we report the case of six children with NMOSD who received PE along with the outcomes and adverse events. All six children (female, age at onset 4 years 9 months–13 years 2 months) were AQP4-IgG positive and received standard PE using the COM.TEC Cell Separator. The interval between NMOSD onset and PE was 29 days (range 10–98). Only one patient (P3) who received PE 10 days after acute exacerbations exhibited clinical improvement. Her left visual acuity increased from 0.06 to 0.6 (spectacle-corrected visual acuity was 1.0) and her EDSS score decreased from 4 to 3 points. The other five patients had no clinical improvement and no EDSS scores changes after PE. Adverse events included rashes (P1, P3), acute non-occlusive thrombosis of the internal jugular vein (P1), and thrombocytopenia (P2). In conclusion, the timing of PE initiation as a rescue therapy for severe and corticosteroid-unresponsive pediatric AQP4-IgG positive NMOSD may be crucial to treatment efficacy, and early initiation of PE may be associated with a better outcome. Furthermore, PE has the potential risk for clinically significant adverse effects that should be considered before initiating the therapy and should be weighed against potential benefits

Ophiostomatoid species associated with pine trees (Pinus spp.) infested by Cryphalus piceae from eastern China, including five new species

Cryphalus piceae attacks various economically important conifers. Similar to other bark beetles, Cr. piceae plays a role as a vector for an assortment of fungi and nematodes. Previously, several ophiostomatoid fungi were isolated from Cr. piceae in Poland and Japan. In the present study, we explored the diversity of ophiostomatoid fungi associated with Cr. piceae infesting pines in the Shandong Province of China. We isolated ophiostomatoid fungi from both galleries and beetles collected from our study sites. These fungal isolates were identified using both molecular and morphological data. In this study, we recovered 175 isolates of ophiostomatoid fungi representing seven species. Ophiostoma ips was the most frequently isolated species. Molecular and morphological data indicated that five ophiostomatoid fungal species recovered were previously undescribed. Thus, we proposed these five novel species as Ceratocystiopsis yantaiensis, C. weihaiensis, Graphilbum translucens, Gr. niveum, and Sporothrix villosa. These new ophiostomatoid fungi add to the increasing number of fungi known from China, and this evidence suggests that numerous novel taxa are awaiting discovery in other forests of China.Shandong Normal University.https://mycokeys.pensoft.netam2022BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Structure-function analysis of CYP719As involved in methylenedioxy bridge-formation in the biosynthesis of benzylisoquinoline alkaloids and its de novo production

Benzylisoquinoline alkaloids (BIAs) are a type of secondary metabolite with clinical application value. (S)-stylopine is a special BIA which contains methylenedioxy bridge structures. CYP719As could catalyze the methylenedioxy bridge-formation on the A or D rings of protoberberine alkaloids, while displaying significant substrate regiospecificity. To explore the substrate preference of CYP719As, we cloned and identified five CyCYP719A candidates from Corydalis yanhusuo. Two CyCYP719As (CyCYP719A39 and CyCYP719A42) with high catalytic efficiency for the methylenedioxy bridge-formation on the D or A rings were characterized, respectively. The residues (Leu 294 for CyCYP719A42 and Asp 289 for CyCYP719A39) were identified as the key to controlling the regioselectivity of CYP719As affecting the methylenedioxy bridge-formation on the A or D rings by homology modeling and mutation analysis. Furthermore, for de novo production of BIAs, CyCYP719A39, CyCYP719A42, and their mutants were introduced into the (S)-scoulerine-producing yeast to produce 32\ua0mg/L (S)-stylopine. These results lay a foundation for understanding the structure-function relationship of CYP719A-mediated methylenedioxy bridge-formation and provide yeast strains for the BIAs production by\ua0synthetic biology

Catalytic promiscuity of O-methyltransferases from Corydalis yanhusuo leading to the structural diversity of benzylisoquinoline alkaloids

O-methyltransferases play essential roles in producing structural diversity and improving the biological properties of benzylisoquinoline alkaloids (BIAs) in plants. In this study, Corydalis yanhusuo, a plant used in traditional Chinese medicine due to the analgesic effects of its BIA-active compounds, was employed to analyze the catalytic characteristics of O-methyltransferases in the formation of BIA diversity. Seven genes encoding O-methyltransferases were cloned, and functionally characterized using seven potential BIA substrates. Specifically, an O-methyltransferase (CyOMT2) with highly efficient catalytic activity of both 4′- and 6-O-methylations of 1-BIAs was found. CyOMT6 was found to perform two sequential methylations at both 9- and 2-positions of the essential intermediate of tetrahydroprotoberberines, (S)-scoulerine. Two O-methyltransferases (CyOMT5 and CyOMT7) with wide substrate promiscuity were found, with the 2-position of tetrahydroprotoberberines as the preferential catalytic site for CyOMT5 (named scoulerine 2-O-methyltransferase) and the 6-position of 1-BIAs as the preferential site for CyOMT7. In addition, results of integrated phylogenetic molecular docking analysis and site-directed mutation suggested that residues at sites 172, 306, 313, and 314 in CyOMT5 are important for enzyme promiscuity related to O-methylations at the 6- and 7-positions of isoquinoline. Cys at site 253 in CyOMT2 was proved to promote the methylation activity of the 6-position and to expand substrate scopes. This work provides insight into O-methyltransferases in producing BIA diversity in C. yanhusuo and genetic elements for producing BIAs by metabolic engineering and synthetic biology

Visible light crosslinkable human hair keratin hydrogels

Abstract Keratins extracted from human hair have emerged as a promising biomaterial for various biomedical applications, partly due to their wide availability, low cost, minimal immune response, and the potential to engineer autologous tissue constructs. However, the fabrication of keratin‐based scaffolds typically relies on limited crosslinking mechanisms, such as via physical interactions or disulfide bond formation, which are time‐consuming and result in relatively poor mechanical strength and stability. Here, we report the preparation of photocrosslinkable keratin‐polyethylene glycol (PEG) hydrogels via the thiol‐norbornene “click” reaction, which can be formed within one minute upon irradiation of visible light. The resulting keratin‐PEG hydrogels showed highly tunable mechanical properties of up to 45 kPa in compressive modulus, and long‐term stability in buffer solutions and cell culture media. These keratin‐based hydrogels were tested as cell culture substrates in both two‐dimensional surface seeding and three‐dimensional cell encapsulation, demonstrating excellent cytocompatibility to support the attachment, spreading, and proliferation of fibroblast cells. Moreover, the photocrosslinking mechanism makes keratin‐based hydrogel suitable for various microfabrication techniques, such as micropatterning and wet spinning, to fabricate cell‐laden tissue constructs with different architectures. We believe that the unique features of this photocrosslinkable human hair keratin hydrogel promise new opportunities for their future biomedical applications