Finite-element modelling of elastic wave propagation and scattering within heterogeneous media

The scattering treated here arises when elastic waves propagate within a heterogeneous medium defined by random spatial fluctuation of its elastic properties. Whereas classical analytical studies are based on lower-order scattering assumptions, numerical methods conversely present no such limitations by inherently incorporating multiple scattering. Until now, studies have typically been limited to two or one dimension, however, owing to computational constraints. This article seizes recent advances to realize a finite-element formulation that solves the three-dimensional elastodynamic scattering problem. The developed methodology enables the fundamental behaviour of scattering in terms of attenuation and dispersion to be studied. In particular, the example of elastic waves propagating within polycrystalline materials is adopted, using Voronoi tessellations to randomly generate representative models. The numerically observed scattering is compared against entirely independent but well-established analytical scattering theory. The quantitative agreement is found to be excellent across previously unvisited scattering regimes; it is believed that this is the first quantitative validation of its kind which provides significant support towards the existence of the transitional scattering regime and facilitates future deployment of numerical methods for these problems

[(3aS,5aR,8aR,8bS)-2,2,7,7-Tetra­methyl­tetra­hydro-3aH-bis­[1,3]dioxolo[4,5-b:4′,5′-d]pyran-3a-yl]methyl (R)-N-(1-phenyl­eth­yl)sulfamate

In the title compound, C20H29NO8S, the two five-membered rings adopt envelope conformations (with an O atom at the flap in each case), while the six-membered pyran ring displays a twist-boat conformation. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds into a supra­molecular chain running along the a axis

A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. Methods In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. Results In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. Conclusions We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC

A Novel Mutation in CRYBB1 Associated with Congenital Cataract-Microcornea Syndrome: The p.Ser129Arg Mutation Destabilizes the βB1/βA3-crystallin Heteromer But Not the βB1-crystallin Homomer

Congenital cataract-microcornea syndrome (CCMC) is a clinically and genetically heterogeneous condition characterized by lens opacities and microcornea. It appears as a distinct phenotype of heritable congenital cataract. Here we report a large Chinese family with autosomal dominant congenital cataract and microcornea. Evidence for linkage was detected at marker D22S1167 (LOD score [Z]=4.49, recombination fraction [θ]=0.0), which closely flanks the â-crystallin gene cluster locus. Direct sequencing of the candidate âB1-crystallin gene (CRYBB1) revealed a c.387C>A transversion in exon 4, which cosegregated with the disease in the family and resulted in the substitution of serine by arginine at codon 129 (p.Ser129Arg). A comparison of the biophysical properties of the recombinant β-crystallins revealed that the mutation impaired the structures of both βB1-crystallin homomer and βB1/βA3-crystallin heteromer. More importantly, the mutation significantly decreased the thermal stability of βB1/βA3-crystallin but not βB1-crystallin. These findings highlight the importance of protein-protein interactions among β-crystallins in maintaining lens transparency, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCMC. © 2011 Wiley-Liss, Inc

Lack of evidence of hepatitis in patients with oral lichen planus in China: a case control study

Background: China has been one of the countries with high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) liver disease. And lichen planus is an extrahepatic manifestation of patients with chronic HCV infection. This case-control study was conducted to investigate the relationship between oral lichen planus (OLP) and HBV/HCV infection in China. Material and Methods: A total of 776 patients, including 150 patients with OLP (Group OLP), 429 inpatients from the Trauma Ward of Oral and Maxillofacial Surgery Department (Group A), 110 patients with other oral mucosal diseases, but without a reported association with HCV infection (Group B) and 87 patients with oral lichenoid lesion (Group OLL), were compared with their seroprevalence of anti-HCV antibody (HCVAb), hepatitis B surface antigen (HBsAg) and the parameters of liver functions. Moreover, the clinical characteristics of OLP were also observed, such as gender, age, chief complaint, course of the disease, clinical type, sites involved and so on. Results: The positive rates of HCVAb and HBsAg in OLP patients were 0.7% and 4%, respectively. Neither HCVAb nor HBsAg was associated with OLP as demonstrated by both the univariate and the multivariate analyses. The clinical features and liver functions of OLP patients with negative or positive HBsAg were nearly the same. Conclusions: Our findings verify that there is no association between OLP and hepatitis and there is no need to run a screening test for HCV or HBV in OLP patients in Chin

Comprehensive Assessment of Toxicity in ChatGPT

Moderating offensive, hateful, and toxic language has always been an important but challenging topic in the domain of safe use in NLP. The emerging large language models (LLMs), such as ChatGPT, can potentially further accentuate this threat. Previous works have discovered that ChatGPT can generate toxic responses using carefully crafted inputs. However, limited research has been done to systematically examine when ChatGPT generates toxic responses. In this paper, we comprehensively evaluate the toxicity in ChatGPT by utilizing instruction-tuning datasets that closely align with real-world scenarios. Our results show that ChatGPT's toxicity varies based on different properties and settings of the prompts, including tasks, domains, length, and languages. Notably, prompts in creative writing tasks can be 2x more likely than others to elicit toxic responses. Prompting in German and Portuguese can also double the response toxicity. Additionally, we discover that certain deliberately toxic prompts, designed in earlier studies, no longer yield harmful responses. We hope our discoveries can guide model developers to better regulate these AI systems and the users to avoid undesirable outputs

Maximizing the accuracy of finite element simulation of elastic wave propagation in polycrystals

Three-dimensional finite element (FE) modelling, with representation of materials at grain scale in realistic sample volumes, is capable of accurately describing elastic wave propagation and scattering within polycrystals. A broader and better future use of this FE method requires several important topics to be fully understood, and this work presents studies addressing this aim. The first topic concerns the determination of effective media parameters, namely, scattering induced attenuation and phase velocity, from measured coherent waves. This work evaluates two determination approaches, through-transmission and fitting, and it is found that these approaches are practically equivalent and can thus be used interchangeably. For the second topic of estimating modelling errors and uncertainties, this work performs thorough analytical and numerical studies to estimate those caused by both FE approximations and statistical considerations. It is demonstrated that the errors and uncertainties can be well suppressed by using a proper combination of modelling parameters. For the last topic of incorporating FE model information into theoretical models, this work presents elaborated investigations and shows that to improve agreement between the FE and theoretical models, the symmetry boundary conditions used in FE models need to be considered in the two-point correlation function, which is required by theoretical models

Decreased CD8+CD28+/CD8+CD28– T cell ratio can sensitively predict poor outcome for patients with complicated Crohn disease

Crohn disease (CD) with complications such as penetrating, stricturing, and perianal disease is called complicated CD. The aim of this study is to test the efficiency with which the CD8+CD28+/CD8+CD28– cell balance can predict a subsequent active stage in patients with newly diagnosed complicated CD. Seventeen patients with complicated CD and 48 CD patients with no complications were enrolled. Blood CD8+ T cells were tested from all of the 65 newly diagnosed CD patients upon enrollment. The potential risk factors were compared between the 2 groups. A 30-week follow-up was performed, and the efficiency of the CD8+ cell balance at predicting active CD was analyzed using receiver- operating characteristic curves. The cumulative remission lasting rates (CRLRs) were analyzed using the Kaplan–Meier method. Compared with the control CD group, patients with complicated CD were predominantly male and younger in age; they also had lower body mass indices (BMIs), higher Crohn disease activity indices (CDAIs), higher immunosuppressant and steroid prescription rates, and significantly higher surgical rates. The CD8+CD28+/CD8+CD28– balance was associated with BMI, CDAI, steroids, and surgery. The CD8+CD28+/CD8+CD28– ratios were significantly lower at week 0 and on the 6th, 22nd, and 30th week during follow- up with a shorter lasting time of remission for the complicated CD patients. The CD8+CD28+/CD8+CD28– ratio could accurately predict the active stage for the patients with complicated CD, and the highest sensitivity (89.2%) and specificity (85.3%) were found when the ratio was 1.03. Treatment with steroids and surgery, along with a significantly lower CD8+CD28+/CD8+CD28– ratio and lower CRLRs, was closely related to a worse outcome for the patients with complicated CD. Patients requiring steroids and surgery experience more severe disease activity and thus a disequilibrated immunological balance, which could be the main reason for a decreased CD8+CD28+/CD8+CD28– ratio. This ratio can sensitively predict the active stage for patients with complicated CD, and more care should be taken when this ratio is <1.03

PX Motif of DNA Binds Specifically to Escherichia coli DNA Polymerase I

The PX motif of DNA is a four-stranded structure in which two parallel juxtaposed double-helical domains are fused by crossovers at every point where the strands approach each other. Consequently, its twist and writhe are approximately half of those of conventional DNA. This property has been shown to relax supercoiled plasmid DNA under circumstances in which head-to-head homology exists within the plasmid; the homology can be either complete homology or every-other-half-turn homology, known as PX homology. It is clearly of interest to establish whether the cell contains proteins that interact with this unusual and possibly functional motif. We have examined Escherichia coli extracts to seek such a protein. We find by gel mobility studies that the PX motif is apparently bound by a cellular component. Fractionation of this binding activity reveals that the component is DNA polymerase I (Pol I). Although the PX motif binds to Pol I, we find that PX-DNA is not able to serve as a substrate for the extension of a shortened strand. We cannot say at this time whether the binding is a coincidence or whether it represents an activity of Pol I that is currently unknown. We have modeled the interaction of Pol I and PX-DNA using symmetry considerations and molecular dynamics