Large deformation of spherical vesicle studied by perturbation theory and Surface evolver

With tangent angle perturbation approach the axial symmetry deformation of a spherical vesicle in large under the pressure changes is studied by the elasticity theory of Helfrich spontaneous curvature model.Three main results in axial symmetry shape: biconcave shape, peanut shape, and one type of myelin are obtained. These axial symmetry morphology deformations are in agreement with those observed in lipsome experiments by dark-field light microscopy [Hotani, J. Mol. Biol. 178, (1984) 113] and in the red blood cell with two thin filaments (myelin) observed in living state (see, Bessis, Living Blood Cells and Their Ultrastructure, Springer-Verlag, 1973). Furthermore, the biconcave shape and peanut shape can be simulated with the help of a powerful software, Surface Evolver [Brakke, Exp. Math. 1, 141 (1992) 141], in which the spontaneous curvature can be easy taken into account.Comment: 16 pages, 6 EPS figures and 2 PS figure

Inactivation of a Novel FGF23 Regulator, FAM20C, Leads to Hypophosphatemic Rickets in Mice

Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the mineralized tissues of mammals. Genetic studies showed that the loss-of-function mutations in FAM20C were associated with human lethal osteosclerotic bone dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone formation. However, in vitro gain- and loss-of-function studies suggested that FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with Fam20c cKO mice to introduce the transgene in the knockout background. In vitro gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1 cells and by lentiviral shRNA–mediated knockdown of FAM20C in human and mouse osteogenic cell lines. Surprisingly, both the global and mineralized tissue-specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis), along with a significant downregulation of osteoblast differentiation markers and a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and bone. The mice expressing the Fam20c transgene in the wild-type background showed no abnormalities, while the expression of the Fam20c transgene fully rescued the skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable downregulation of DMP1, along with a significant upregulation of FGF23 in both human and mouse osteogenic cell lines. These results indicate that FAM20C is a bone formation “promoter” but not an “inhibitor” in mouse osteogenesis. We conclude that FAM20C may regulate osteogenesis through its direct role in facilitating osteoblast differentiation and its systemic regulation of phosphate homeostasis via the mediation of FGF23

Multicolor Combinatorial Probe Coding for Real-Time PCR

The target volume of multiplex real-time PCR assays is limited by the number of fluorescent dyes available and the number of fluorescence acquisition channels present in the PCR instrument. We hereby explored a probe labeling strategy that significantly increased the target volume of real-time PCR detection in one reaction. The labeling paradigm, termed “Multicolor Combinatorial Probe Coding” (MCPC), uses a limited number (n) of differently colored fluorophores in various combinations to label each probe, enabling one of 2n-1 genetic targets to be detected in one reaction. The proof-of-principle of MCPC was validated by identification of one of each possible 15 human papillomavirus types, which is the maximum target number theoretically detectable by MCPC with a 4-color channel instrument, in one reaction. MCPC was then improved from a one-primer-pair setting to a multiple-primer-pair format through Homo-Tag Assisted Non-Dimer (HAND) system to allow multiple primer pairs to be included in one reaction. This improvement was demonstrated via identification of one of the possible 10 foodborne pathogen candidates with 10 pairs of primers included in one reaction, which had limit of detection equivalent to the uniplex PCR. MCPC was further explored in detecting combined genotypes of five β-globin gene mutations where multiple targets were co-amplified. MCPC strategy could expand the scope of real-time PCR assays in applications which are unachievable by current labeling strategy

Tetrahedral mesh improvement by shell transformation

Existing flips for tetrahedral meshes simply make a selection from a few possible configurations within a single shell (i.e., a polyhedron that can be filled up with a mesh composed of a set of elements that meet each other at one edge), and their effectiveness is usually confined. A new topological operation for tetrahedral meshes named shell transformation is proposed. Its recursive callings execute a sequence of shell transformations on neighboring shells, acting like composite edge removal transformations. Such topological transformations are able to perform on a much larger element set than that of a single flip, thereby leading the way towards a better local optimum solution. Hence, a new mesh improvement algorithm is developed by combining this recursive scheme with other schemes, including smoothing, point insertion and point suppression. Numerical experiments reveal that the proposed algorithm can well balance some stringent and yet sometimes even conflict requirements of mesh improvement, i.e., resulting in high-quality meshes and reducing computing time at the same time. Therefore, it can be used for mesh quality improvement tasks involving millions of elements, in which it is essential not only to generate high-quality meshes, but also to reduce total computational time for mesh improvement

Performance of Detecting IgM Antibodies against Enterovirus 71 for Early Diagnosis

Enterovirus 71 (EV71) infection is more likely to induce severe complications and mortality than other enteroviruses. Methods for detection of IgM antibody against EV71 had been established for years, however, the performance of the methods in the very early diagnosis of EV71 infection had not been fully evaluated, which is especially meaningful because of the short incubation period of EV71 infection. In this report, the performance of an IgM anti-EV71 assay was evaluated using acute sera collected from 165 EV71 infected patients, 165 patients infected with other enteroviruses, and more than 2,000 sera from healthy children or children with other infected diseases. The results showed a 90% sensitivity in 20 patients who were in their first illness day, and similar sensitivity remained till 4 days after onset. After then the sensitivity increased to 95% to 100% for more than one month. The specificity of the assay in non-HFMD children is 99.1% (95% CI: 98.6–99.4), similar as the 99.9% specificity in healthy adults. The cross-reaction rate in patients infected with other non-EV71 enteroviruses was 11.4%. In conclusion, the data here presented show that the detection of IgM anti-EV71 by ELISA affords a reliable, convenient, and prompt diagnosis of EV71 infection

Timing of uplift and evolution of the Lüliang Mountains, North China Craton

This study analyses evidence for reformed basin development and basin-mountain coupling associated with development of the Ordos Basin and the Lüliang Mountains, China. Gaining an improved understanding of the timing and nature of uplift and evolution of the Lüliang Mountains is important for the reconstruction of the eastern sedimentary boundary of the Ordos Basin (a major petroliferous basin) as well as for providing insight into the evolution and breakup of the North China Craton (NCC). Based on systematic sampling for fission track analysis, it is suggested that the main phase of uplift of the Lüliang Mountains occurred since later part of the Early Cretaceous. Three evolutionary stages of uplift and development are identified: slow initial uplift (120–65 Ma), accelerated uplift (65–23 Ma), and intensive uplift (23 Ma to present), with the majority of the uplift activity having occurred during the Cenozoic. The history of uplift is non-equilibrium and exhibits complexity in temporal and spatial aspects. The middle and northern parts of the Lüliang Mountains were uplifted earlier than the southern part. The most intensive episode of uplift activity commenced in the Miocene and was associated with a genetic coupling relationship with the eastern neighboring Cenozoic Shanxi Grabens. The uplifting and evolutionary processes of the Lüliang Mountains area since later part of the Early Cretaceous share a unified regional geodynamic setting, which was accompanied by uplift of the Mesozoic Ordos Basin and development of the neighboring Cenozoic Shanxi Grabens. Collectively, this regional orogenic activity is related principally to the far-field effects of both the compression sourced from the southwestern Tibet Plateau and westward subduction of the Pacific Plate in Cenozoic

ESR1 and EGF genetic variation in relation to breast cancer risk and survival

The main purposes of this thesis were to analyse common genetic variation in candidate genes and candidate pathways in relation to breast cancer risk, prognosticators and survival, to develop statistical methods for genetic association analysis for evaluating the joint importance of genes, and to investigate the potential impact of adding genetic information to clinical risk factors for projecting individualised risk of developing breast cancer over specific time periods. In Paper I we studied genetic variation in the estrogen receptor α and epidermal growth factor genes in relation to breast cancer risk and survival. We located a region in the estrogen receptor α gene which showed a moderate signal for association with breast cancer risk but were unable to link common variation in the epidermal growth factor gene with breast cancer aetiology or prognosis. In Paper II we investigated whether suspected breast cancer risk SNPs within genes involved in androgen-to-estrogen conversion are associated with breast cancer prognosticators grade, lymph node status and tumour size. The strongest association was observed for a marker within the CYP19A1 gene with histological grade. We also found evidence that a second marker from the same gene is associated with histological grade and tumour size. In Paper III we developed a novel test of association which incorporates multivariate measures of categorical and continuous heterogeneity. In this work we described both a single-SNP and a global multi-SNP test and used simulated data to demonstrate the power of the tests when genetic effects differ across disease subtypes. In Paper IV we assessed the extent to which recently associated genetic risk variants improve breast cancer risk-assessment models. We investigated empirically the performance of eighteen breast cancer risk SNPs together with mammographic density and clinical risk factors in predicting absolute risk of breast cancer. We also examined the usefulness of various prediction models considered at a population level for a variety of individualised breast cancer screening approaches. The goal of a genetic association study is to establish statistical associations between genetic variants and disease states. Each variant linked to a disease can lead the way to a better understanding of the underlying biological mechanisms that govern the development of a disease. Increased knowledge of molecular variation provides the opportunity to stratify populations according to genetic makeup, which in turn has the potential to lead to improved disease prevention programs and improved patient care

Dynamic model of basic oxygen steelmaking process based on multi-zone reaction kinetics : model derivation and validation

A multi-zone kinetic model coupled with a dynamic slag generation model was developed for the simulation of hot metal and slag composition during the BOF operation. The three reaction zones, (i) jet impact zone (ii) slag-bulk metal zone (iii) slag-metal-gas emulsion zone were considered for the calculation of overall refining kinetics. In the rate equations, the transient rate parameters were mathematically described as a function of process variables. A micro and macroscopic rate calculation methodology (micro-kinetics and macro-kinetics) were developed to estimate the total refining contributed by the recirculating metal droplets through the slag-metal emulsion zone. The micro-kinetics involves developing the rate equation for individual droplets in the emulsion. The mathematical models for the size distribution of initial droplets, kinetics of simultaneous refining of elements, the residence time in the emulsion, dynamic interfacial area change were established in the micro-kinetic model. In the macro-kinetics calculation, a droplet generation model was employed and the total amount of refining by emulsion was calculated by summing the refining from the entire population of returning droplets. A dynamic FetO generation model based on oxygen mass balance was developed and coupled with the multi-zone kinetic model. The effect of post combustion on the evolution of slag and metal composition was investigated. The model was applied to a 200-ton top blowing converter and the simulated value of metal and slag was found to be in good agreement with the measured data. The post-combustion ratio was found to be an important factor in controlling FetO content in the slag and the kinetics of Mn and P in a BOF process