An Open Platform for Processing IFC Model Versions

The IFC initiative from the International Alliance of Interoperability has been developing since the mid-nineties through several versions. This paper addresses the problem of binding the growing number of IFC versions and their EXPRESS definitions to programming environments (Java and .NET). The solution developed in this paper automates the process of generating early binding classes, whenever a new version of the IFC model is released. Furthermore, a runtime instantiation of the generated early binding classes takes place by importing IFC-STEP ISO 10303-P21 models. The user can navigate the IFC STEP model with relevance to the defining EXPRESS-schema, modify, delete, and create new instances. These functionalities are considered to be a basis for any IFC based implementation. It enables researchers to experiment the IFC model independently from any software application.     

The concentration of ammonia in the excreta of sixth instar larvae ofLamida moncusalis Walker (Pyralidae: Lepidoptera) during development

Summary The concentration of ammonia in the fresh and dry excreta ofLamida moncusalis Walker was determined. It was found that a large quantity of ammonia was lost from the excreta on drying. Ammonia is one of the major excretory products of the larva.5 September 1986Acknowledgment. We thank the State Committee on Science, Technology and Environment, Kerala, for the financial assistance.     

NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens

Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of nuclear factor-κB (NF-κB), type I interferon and inflammasome signalling. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis, but the role of NLRP6 in microbial infections and the nature of the inflammatory signalling pathways regulated by NLRP6 remain unclear. Here we show that Nlrp6-deficient mice are highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signalling in both haematopoietic and radioresistant cells contributed to increased susceptibility. Nlrp6 deficiency enhanced activation of mitogen-activated protein kinase (MAPK) and the canonical NF-κB pathway after Toll-like receptor ligation, but not cytosolic NOD1/2 ligation, in vitro. Consequently, infected Nlrp6-deficient cells produced increased levels of NF-κB- and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signalling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and -negative bacterial pathogens.     

Mutations in SECISBP2 result in abnormal thyroid hormone metabolism

Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins. Mice lacking tRNA(Sec) die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans. Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. We identified three of seven siblings with clinical evidence of abnormal thyroid hormone metabolism. Their fibroblasts showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. Systematic linkage analysis of genes involved in DIO2 synthesis and degradation led to the identification of an inherited Sec incorporation defect, caused by a homozygous missense mutation in SECISBP2 (also called SBP2). An unrelated child with a similar phenotype was compound heterozygous with respect to mutations in SECISBP2. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.     

A mechanosensory complex that mediates the endothelial cell response to fluid shear stress

Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis, but the mechanisms of transduction are poorly understood. Previous work showed that the conversion of integrins to a high-affinity state mediates a subset of shear responses, including cell alignment and gene expression. Here we investigate the pathway upstream of integrin activation. PECAM-1 (which directly transmits mechanical force), vascular endothelial cell cadherin (which functions as an adaptor) and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) comprise a mechanosensory complex. Together, these receptors are sufficient to confer responsiveness to flow in heterologous cells. In support of the relevance of this pathway in vivo, PECAM-1-knockout mice do not activate NF-kappaB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.     

Preparation of bioactive glasses with controllable degradation behavior and their bioactive characterization

Bioactive glasses and ceramics have been widely investigated for bone repair because of their excel-lent bioactive characteristics. However, these biomaterials undergo incomplete conversion into a bone-like material, which severely limits their biomedical application. In this paper, borosilicate bioac-tive glasses were prepared by traditional melting process. The results showed that borosilicate glasses possessed high biocompatibility and bioactivity. In addition, when immersed in a 0.02 mol/L K2HPO4 solution, particles of a borate glass were fully converted to HA. The desirable conversion rate to HA may be achieved through the adjustment of the B2O3/SiO2 ratio. The results of XRD and FTIR analysis indicated that the degradation product was carbonate-substituted hydroxyapatite, which was similar to the inorganic component of bone.     

用参数化法简化多元间歇精馏塔的操作优化

考虑了塔板的效率及水力学特性,建立了基于相对挥发度的各板汽液平衡关系。以回流比为操作变量,以单位时间获取最大产量为优化的目标函数。产品的平均浓度以终端函数的形式出现在目标函数中。采用参数化方法化无穷维优化问题为有穷维优化问题,并用改良罚函数和变量置换的方法处理不等式约束,最后用POWELL法搜索最优解。在仿真实验中获得了满意的结果并比较了最优恒回流比和最优变回流比的控制策略的差别。     

Identification of cells initiating human melanomas

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.