Reduced-order modeling of a sliding ring on an elastic rod with incremental potential formulation

Mechanical interactions between rigid rings and flexible cables are widespread in both daily life (hanging clothes) and engineering system (closing a tether net). A reduced-order method for the dynamic analysis of sliding rings on a deformable one-dimensional (1D) rod-like object is proposed. In contrast to discretize the joint rings into multiple nodes and edges for contact detection and numerical simulation, a single point is used to reduce the order of the numerical model. In order to achieve the non-deviation condition between sliding ring and flexible rod, a novel barrier functional is derived based on incremental potential theory, and the tangent frictional interplay is later procured by a lagged dissipative formulation. The proposed barrier functional and the associated frictional functional are $C^{2}$ continuous, hence the nonlinear elastodynamic system can be solved variationally by an implicit time-stepping scheme. The numerical framework is first applied to simple examples where the analytical solutions are available for validation. Then, multiple complex practical engineering examples are considered to showcase the effectiveness of the proposed method. The simplified ring-to-rod interaction model can provide lifelike visual effect for picture animations, and also can support the optimal design for space debris removal system.Comment: 15 pages, 9 figure

3D biofabrication for tubular tissue engineering

The therapeutic replacement of diseased tubular tissue is hindered by the availability and suitability of current donor, autologous and synthetically derived protheses. Artificially created, tissue engineered, constructs have the potential to alleviate these concerns with reduced auto-immune response, high anatomical accuracy, long term patency and growth potential. The advent of 3D bio-printing technology has further supplemented the technological toolbox, opening up new biofabrication research opportunities and expanding the therapeutic potential of the field. In this review, we highlight the challenges facing those seeking to create artificial tubular tissue with its associated complex macro and microscopic architecture. Current biofabrication approaches, including 3D printing techniques, are reviewed and future directions suggested

Constructing tissue-like complex structures using cell-laden DNA hydrogel bricks

Tissue engineering has long been a challenge because of the difficulty of addressing the requirements that such an engineered tissue must meet. In this paper, we developed a new "brick-to-wall" based on unique properties of DNA supramolecular hydrogels to fabricate three-dimensional (3D) tissuelike structures: different cell types are encapsulated in DNA hydrogel bricks which are then combined to build 3D structures. Signal responsiveness of cells through the DNA gels was evaluated and it was discovered that the gel permits cell migration in 3D. The results demonstrated that this technology is convenient, effective and reliable for cell manipulation, and we believe that it will benefit artificial tissue fabrication and future large-scale production

Genetic testing of PAX8 mutations associated with thyroid dysgenesis in Chinese congenital hypothyroidism patients

Introduction: Thyroid dysgenesis (TD) is the main cause of congenital hypothyroidism (CH), affecting nearly 1 in 2000–3000 newborns worldwide, as the most common neonatal endocrine disorder. Paired box gene 8 (PAX8), expressed during all stages of thyroid follicular cell, plays a key role in thyroid morphogenesis by a complex regulatory network. In conclusion, the genetic mechanism of PAX8 mutant in TD is still ambiguous; therefore, further research is needed. Material and methods: Blood samples were collected from 289 TD patients in Shandong Province, China. Genomic DNA was extracted from peripheral blood. All the exons of PAX8 along with their exon-intro boundaries were amplified by PCR and analysed by Sanger sequencing. Results: We identified three novel PAX8 nonsense mutations in three patients by sequence analysis of PAX8: Patient 1 (c.285C>G, p.Tyr95Ter), Patient 2 (c.747T>G, p.Tyr249Ter), and Patient 3 (c.786C>A, p.Tyr262Ter). All the three patients carrying PAX8 variants had obvious clinical phenotypes of thyroid anomaly, such as hypoplasia and athyreosis. Conclusion: We conducted the largest worldwide PAX8 mutation screening so far in TD patients. Three presumably pathogenic PAX8 mutations were detected in 289 TD cases for the first time, showing the mutation rate of PAX8 is 1.04% in Chinese TD patients. In addition, our study expands the gene mutation spectrum of TD

Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue. Three-dimensional (3D) printing offers a method of fabricating complex anatomical features of clinically relevant sizes. However, the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging. This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions. The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional (2D). The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices, which were arrayed. These 2D slices with each layer of a defined pattern were laser cut, and then successfully assembled with varying thicknesses of 100 μm or 200 μm. It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions, where the clinically relevant sizes ranging from a simple cube of 20 mm dimension, to a more complex, 50 mm-tall human ears were created. In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure. The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice, where a range of hole diameters from 200 μm to 500 μm were laser cut in an array where cell confluence values of at least 85% were found at three weeks. Cells were also seeded onto a simpler stacked construct, albeit made with micromachined poly fibre mesh, where cells can be found to migrate through the stack better with collagen as bioadhesives. This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future

适体标记银纳米团簇用于细胞图像和体外粘蛋白1检测。

Development of specific cell imaging technology for accurate tumor early diagnosis and evaluation of drug therapeutic efficiency is in great demand. In this study, a simple and sensitive fluorescence method for Mucin1 (MUC1) image in situ and quantitative assay in vitro has been established using APT-tagged silver nanoclusters (APT-Agnes) containing a recognition unit of MUC1 aptamer as the label-free fluorescence probe. The principle of the method is that specific recognition and binding of MUC1 with aptamer can result in the fluorescence quenching of APT-Agnes. The method for MUC1 assay showed a linear range from 0.1 to 100 NM with a limit of detection of 0.05 nM. Furthermore, the fluorescent probe of APT-AgNCs was successfully used for detection of MUC1 in serum and MCF-7 cell imaging. In our point, the above results demonstrated that the new simple method provided an alternative for direct quantitative assay of MUC1 in homogeneous solution and cell imaging, which is helpful for biomedical study and clinical diagnosis related with MUC1

Investigation of a Possible Role for the Histidine Decarboxylase Gene in Tourette Syndrome in the Chinese Han Population: A Family-Based Study.

Tourette syndrome (TS) is a polygenic neuropsychiatric disease. Previous studies have indicated that dysregulation in the histaminergic system may play a crucial role in disease onset. In this study, we investigated the role of the histidine decarboxylase gene (HDC) in TS susceptibility in the Chinese Han population. After genotyping 241 TS nuclear families trios, we analyzed three tag HDC single nucleotide polymorphisms (rs854150, rs854151, and rs854157) in a family-based study using the transmission disequilibrium test (TDT) and haplotype relative risk (HRR). TDT showed no over-transmission in these SNPs across the HDC region (for rs854150: χ2 = 0.472, P = 0.537, OR = 1.097, 95%CI = 0.738-1.630; for rs854151: χ2 = 0.043, P = 0.889, OR = 1.145, 95%CI = 0.767-1.709; for rs854157:χ2 = 0.984, P = 0.367, OR = 1.020, 95%CI = 0.508-2.049). HRR also showed the same tendency (for rs854150: χ2 = 0.211, P = 0.646, OR = 1.088, 95%CI = 0.759-1.559; for rs854151: χ2 = 0.134, P = 0.714, OR = 0.935, 95%CI = 0.653-1.339; for rs854157:χ2 = 0.841, P = 0.359, OR = 1.206, 95%CI = 0.808-1.799). Additionally, the haplotype-based haplotype relative risk showed a negative association. Although these findings indicate an unlikely association between HDC and TS in the Chinese Han population, a potential role for HDC cannot be ruled out in TS etiology. Future research should investigate this more thoroughly using different populations and larger samples

Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis

Abstract Background Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI