101 research outputs found

    Analysis of rolling in high-strength structural steel plates (S690QL)

    Get PDF
    La investigación calcula las condiciones del proceso de rolado en una máquina cilindradora de 3 rodillos. Inicialmente se determina de forma experimental la estructura y propiedades mecánicas del acero de alta resistencia a procesar. Luego se establecieron las ecuaciones que permiten determinar relaciones entre el espesor y el ancho del acero a cilindrar, considerando las características de resistencia de la máquina cilindradora. Finalmente se presentan las gráficas que ayudan al procesamiento eficiente y adecuado del acero escogiendo el ancho/alto y la fuerza requerida para el conformado de la placa de acuerdo a su espesor. La información obtenida permitirá que desde el proceso de diseño de una pieza a fabricar se pueda contemplar el número de juntas de soladura que se necesitan para obtener la altura/largo final del componente.The research calculates the rolling process conditions in a 3-roll bending machine. Initially, structure and mechanical properties of the highstrength steel to be processed are determined in an experimental manner. Then, equations that allow determining the relationship between thickness and width of the steel to be bent are established, taking into consideration strength features of the bending machine. Finally, some graphs that help achieving an efficient and adequate processing of the steel are presented, choosing width/height and strength required for the plate forming, according to its thickness. The information obtained will allow having a number of welding joints needed to obtain final height/length of the component, from the design process of a part to be formed

    ISAP-MATLAB Package for Sensitivity Analysis of High-Dimensional Stochastic Chemical Networks

    Get PDF
    Stochastic simulation and modeling play an important role to elucidate the fundamental mechanisms in complex biochemical networks. The parametric sensitivity analysis of reaction networks becomes a powerful mathematical and computational tool, yielding information regarding the robustness and the identifiability of model parameters. However, due to overwhelming computational cost, parametric sensitivity analysis is a extremely challenging problem for stochastic models with a high-dimensional parameter space and for which existing approaches are very slow. Here we present an information-theoretic sensitivity analysis in path-space (ISAP) MATLAB package that simulates stochastic processes with various algorithms and most importantly implements a gradient-free approach to quantify the parameter sensitivities of stochastic chemical reaction network dynamics using the pathwise Fisher information matrix (PFIM; Pantazis, Katsoulakis, and Vlachos 2013). The sparse, block-diagonal structure of the PFIM makes its computational complexity scale linearly with the number of model parameters. As a result of the gradientfree and the sparse nature of the PFIM, it is highly suitable for the sensitivity analysis of stochastic reaction networks with a very large number of model parameters, which are typical in the modeling and simulation of complex biochemical phenomena. Finally, the PFIM provides a fast sensitivity screening method (Arampatzis, Katsoulakis, and Pantazis 2015) which allows it to be combined with any existing sensitivity analysis software

    Evolution of Publications, Subjects, and Co-authorships in Network-On-Chip Research From a Complex Network Perspective

    Get PDF
    The academia and industry have been pursuing network-on-chip (NoC) related research since two decades ago when there was an urgency to respond to the scaling and technological challenges imposed on intra-chip communication in SoC designs. Like any other research topic, NoC inevitably goes through its life cycle: A. it started up (2000-2007) and quickly gained traction in its own right; B. it then entered the phase of growth and shakeout (2008-2013) with the research outcomes peaked in 2010 and remained high for another four/five years; C. NoC research was considered mature and stable (2014-2020), with signs showing a steady slowdown. Although from time to time, excellent survey articles on different subjects/aspects of NoC appeared in the open literature, yet there is no general consensus on where we are in this NoC roadmap and where we are heading, largely due to lack of an overarching methodology and tool to assess and quantify the research outcomes and evolution. In this paper, we address this issue from the perspective of three specific complex networks, namely the citation network, the subject citation network, and the co-authorship network. The network structure parameters (e.g., modularity, diameter, etc.) and graph dynamics of the three networks are extracted and analyzed, which helps reveal and explain the reasons and the driving forces behind all the changes observed in NoC research over 20 years. Additional analyses are performed in this study to link interesting phenomena surrounding the NoC area. They include: (1) relationships between communities in citation networks and NoC subjects, (2) measure and visualization of a subject\u27s influence score and its evolution, (3) knowledge flow among the six most popular NoC subjects and their relationships, (4) evolution of various subjects in terms of number of publications, (5) collaboration patterns and cross-community collaboration among the authors in NoC research, (6) interesting observation of career lifetime and productivity among NoC researchers, and finally (7) investigation of whether or not new authors are chasing hot subjects in NoC. All these analyses have led to a prediction of publications, subjects, and co-authorship in NoC research in the near future, which is also presented in the paper

    Novel HLA-DRB1 alleles contribute risk for disease susceptibility in primary biliary cholangitis

    Get PDF
    Background: Primary biliary cholangitis (PBC) is a complex disease with high heritability. We investigated the association between human leukocyte antigen (HLA)-DRB1 alleles and PBC in families and sporadic cases to evaluate the genetic components of the disease. Methods: We performed whole exome sequencing in three PBC families. We genotyped HLA-DRB1 and calculated the association between HLA-DRB1 alleles and the encoding amino acid sequences with the clinical features. Results: Ten variants harboured the HLA-DRB1 gene associated with PBC. DRB1 x07:01, 14:01 and 14:05 were highly increased in PBC. Ten coding region polymorphisms were associated with PBC that encode the amino acid variants of HLA-DR beta 54, beta 59 and beta 66 located in the peptide-binding site of the MHC molecule. Glutamine at position 54 was confirmed as a risk amino acid, verifying the results of familial aggregation analysis of PBC families. Discussion: Familial aggregation analysis indicated that HLA-DRB1 is a candidate gene for the risk of disease course. Considering that amino acid variations are critical to peptide-binding properties, they underlie the major component of MHC association with PBC. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

    Virulence Determinants Are Required for Brain Abscess Formation Through Staphylococcus aureus Infection and Are Potential Targets of Antivirulence Factor Therapy

    Get PDF
    Bacterial brain abscesses (BAs) are difficult to treat with conventional antibiotics. Thus, the development of alternative therapeutic strategies for BAs is of high priority. Identifying the virulence determinants that contribute to BA formation induced by Staphylococcus aureus would improve the effectiveness of interventions for this disease. In this study, RT-qPCR was performed to compare the expression levels of 42 putative virulence determinants of S. aureus strains Newman and XQ during murine BA formation, ear colonization, and bacteremia. The alterations in the expression levels of 23 genes were further confirmed through specific TaqMan RT-qPCR. Eleven S. aureus genes that persistently upregulated expression levels during BA infection were identified, and their functions in BA formation were confirmed through isogenic mutant experiments. Bacterial loads and BA volumes in mice infected with isdA, isdC, lgt, hla, or spa deletion mutants and the hla/spa double mutant strain were lower than those in mice infected with the wild-type Newman strain. The therapeutic application of monoclonal antibodies against Hla and SpA decreased bacterial loads and BA volume in mice infected with Newman. This study provides insights into the virulence determinants that contribute to staphylococcal BA formation and a paradigm for antivirulence factor therapy against S. aureus infections

    Pushing the Limits of Machine Design: Automated CPU Design with AI

    Full text link
    Design activity -- constructing an artifact description satisfying given goals and constraints -- distinguishes humanity from other animals and traditional machines, and endowing machines with design abilities at the human level or beyond has been a long-term pursuit. Though machines have already demonstrated their abilities in designing new materials, proteins, and computer programs with advanced artificial intelligence (AI) techniques, the search space for designing such objects is relatively small, and thus, "Can machines design like humans?" remains an open question. To explore the boundary of machine design, here we present a new AI approach to automatically design a central processing unit (CPU), the brain of a computer, and one of the world's most intricate devices humanity have ever designed. This approach generates the circuit logic, which is represented by a graph structure called Binary Speculation Diagram (BSD), of the CPU design from only external input-output observations instead of formal program code. During the generation of BSD, Monte Carlo-based expansion and the distance of Boolean functions are used to guarantee accuracy and efficiency, respectively. By efficiently exploring a search space of unprecedented size 10^{10^{540}}, which is the largest one of all machine-designed objects to our best knowledge, and thus pushing the limits of machine design, our approach generates an industrial-scale RISC-V CPU within only 5 hours. The taped-out CPU successfully runs the Linux operating system and performs comparably against the human-designed Intel 80486SX CPU. In addition to learning the world's first CPU only from input-output observations, which may reform the semiconductor industry by significantly reducing the design cycle, our approach even autonomously discovers human knowledge of the von Neumann architecture.Comment: 28 page

    Loaded delta-hemolysin shapes the properties of Staphylococcus aureus membrane vesicles

    Get PDF
    BackgroundMembrane vesicles (MVs) are nanoscale vesicular structures produced by bacteria during their growth in vitro and in vivo. Some bacterial components can be loaded in bacterial MVs, but the roles of the loaded MV molecules are unclear.MethodsMVs of Staphylococcus aureus RN4220 and its derivatives were prepared. Dynamic light scattering analysis was used to evaluate the size distribution, and 4D-label-free liquid chromatography–tandem mass spectrometry analysis was performed to detect protein composition in the MVs. The site-mutation S. aureus RN4220-Δhld and agrA deletion mutant RN4220-ΔagrA were generated via allelic replacement strategies. A hemolysis assay was performed with rabbit red blood cells. CCK-8 and lactate dehydrogenase release assays were used to determine the cytotoxicity of S. aureus MVs against RAW264.7 macrophages. The serum levels of inflammatory factors such as IL-6, IL-1β, and TNFα in mice treated with S. aureus MVs were detected with an enzyme-linked immunosorbent assay kit.ResultsDelta-hemolysin (Hld) was identified as a major loaded factor in S. aureus MVs. Further study showed that Hld could promote the production of staphylococcal MVs with smaller sizes. Loaded Hld affected the diversity of loaded proteins in MVs of S. aureus RN4220. Hld resulted in decreased protein diversity in MVs of S. aureus. Site-mutation (RN4220-Δhld) and agrA deletion (RN4220-ΔagrA) mutants produced MVs (ΔhldMVs and ΔagrAMVs) with a greater number of bacterial proteins than those derived from wild-type RN4220 (wtMVs). Moreover, Hld contributed to the hemolytic activity of wtMVs. Hld-loaded wtMVs were cytotoxic to macrophage RAW264.7 cells and could stimulate the production of inflammatory factor IL-6 in vivo.ConclusionThis study presented that Hld was a major loaded factor in S. aureus MVs, and the loaded Hld played vital roles in the MV-property modification

    High prevalence of Rickettsia spp. in ticks from wild hedgehogs rather than domestic bovine in Jiangsu province, Eastern China

    Get PDF
    BackgroundSpotted fever group Rickettsia (SFGR), containing various pathogenic Rickettsia spp., poses remarkable negative influences to public health by causing various severe or mild diseases. Information regarding prevalence of SFGR in ticks in Jiangsu province, Eastern China, is still limited and needs urgent investigations.MethodsHedgehog- and bovine-attached ticks were collected from Jiangsu province, Eastern China. DNA of individual ticks was extracted for nested polymerase chain reaction amplifications targeting gltA, 16S ribosomal RNA (rrs), ompA, ompB, and sca4 genes following with sequencing. SFGR-specific IgG antibodies in sera of local donators were evaluated using ELISA.ResultsOverall, 144 (83.2%) of the 173 ticks from hedgehogs and 2 (1.2%) of the 168 ticks from bovine were positive for one of the three identified Rickettsia spp., with significant difference between the two groups (P = 3.6e-52). Candidatus Rickettsia principis (9; 5.2%) and R. heilongjiangensis (135; 78.0%) were detected in Haemaphysalis flava rather than in H. longicornis ticks from hedgehogs. R. heilongjiangensis (1; 0.6%) and Candidatus R. jingxinensis (or Candidatus R. longicornii) (1; 0.6%) were identified in H. longicornis and Rhipicephalus microplus ticks from bovine, respectively. Phylogenetic analysis indicated Candidatus R. jingxinensis belonged to R. japonica subgroup, whereas Candidatus R. principis belonged to a novel subgroup. Higher serological prevalence of spotted fever and SFGR-specific IgG antibody level in humans were observed around the investigated area than in urban areas, without significant difference.ConclusionCandidatus R. principis and Candidatus R. jingxinensis were identified in Jiangsu province, Eastern China, and fully genetically characterized for the first time. The higher prevalence of SFGR in hedgehog-attached ticks as well as the higher SFGR-specific IgG antibody level and seropositive rate in humans around the investigated area suggested that more attention should be paid to SFGR. This pathogen is usually transmitted or harbored by wild animals and ticks. This study provides important epidemiological data for both physicians and public health officers in developing early prevention and control strategies against potential Rickettsia infections and in the preparation of suitable testing and treatment needs for rickettsiosis in the endemic areas
    • …
    corecore