TIFA, an inflammatory signaling adaptor, is tumor suppressive for liver cancer.

TIFA (TNF receptor associated factor (TRAF)-interacting protein with a Forkhead-associated (FHA) domain), also called T2BP, was first identified using a yeast two-hybrid screening. TIFA contains a FHA domain, which directly binds phosphothreonine and phosphoserine, and a consensus TRAF6-binding motif. TIFA-mediated oligomerization and poly-ubiquitinylation of TRAF6 mediates signaling downstream of the Tumor necrosis factor alpha receptor 1 (TNFaR-I) and interleukin-1/Toll-like receptor 4 (TLR4) pathways. Examining TIFA expression in hepatocellular carcinoma (HCC) tissues microarrays, we noted marked decreases TIFA reactivity in tumor versus control samples. In agreement, we found that HCC cell lines show reduced TIFA expression levels versus normal liver controls. Reconstituting TIFA expression in HCC cell lines promoted two independent apoptosis signaling pathways: the induction of p53 and cell cycle arrest, and the activation of caspase-8 and caspase-3. In contrast, the expression of a non-oligomerizing mutant of TIFA impacted cells minimally, and suppression of TIFA expression protected cells from apoptosis. Mice bearing TIFA overexpression hepatocellular xenografts develop smaller tumors versus TIFA mutant tumors; terminal deoxynucleotidyl transferase dUTP nick end labeling staining demonstrates increased cell apoptosis, and decreased proliferation, reflecting cell cycle arrest. Interestingly, p53 has a greater role in decreased proliferation than cell death, as it appeared dispensable for TIFA-induced cell killing. The findings demonstrate a novel suppressive role of TIFA in HCC progression via promotion of cell death independent of p53

Spatially-optimised fibre-reinforced composites with isosurface-controlled additive manufacturing constraints

A design approach accounting for manufac- turing constraints is described for spatially-optimised fibre-reinforced composites. The approach is based on the optimisation of local fibre orientation, the fibre vol- ume fraction and density based topology optimisation to determine the optimal design. A continuity equation is adopted to constrain the fibre orientation and ensure continuous fibres within the bounds of realistic fibre volume fractions. This results in a fibre orientation with a corresponding and controllable variation of the fibre volume fraction. In order to ensure the continuous fibre can be deposited, the manufacturability of the optimised results is ensured by introducing constraints controlled with two scalar fields to reconstruct fibre paths which are able to provide sufficient information to generate printer toolpaths. A cantilever beam problem is solved to show the advantage of the fibre reinforcement, the inclusion of manufacturing constraints, and the penalty in compliance due to the application of the manufac- turing constraints. The results show that the presented approach successfully guarantees the manufacturability with minimal loss of performance

Introducing mobile home agents into the distributed authentication protocol to achieve location privacy in mobile IPv6

Mobile IPv6 will be the basis for the fourth generation 4G networks which will completely revolutionize the way telecommunication devices operate. This paradigm shift will occur due to the sole use of packed switching networks. Mobile IPv6 utilizes binding updates as a route optimization to reduced triangle routing between the mobile node, the home agent and the correspondent node, allowing direct communication between the mobile node and the correspondent. However, direct communication between the nodes produces a range of security vulnerabilities, which the home agent avoided. This paper attempts to provide the advantages of using the home agent as an intermediary whilst reducing the latency of triangle routing. This can be achieved with the proposed use of a mobile home agent which essentially follows the mobile node as it moves between points of attachment providing location privacy and pseudo-direct communication, which can be incorporated into the distributed authentication protocol or be used as a stand alone solution

Geographic variation in life-history traits : growth season affects age structure, egg size and clutch size in Andrew’s toad (Bufo andrewsi)

Background: Environmental variation associated with season length is likely to promote differentiation in lifehistory traits, but has been little studied in natural populations of ectotherms. We investigated patterns of variation in egg size, clutch size, age at sexual maturity, maximum age, mean age, growth rate and adult body size in relation to growth season length among 17 populations of Andrew’s toad (Bufo andrewsi) at different latitudes and altitudes in the Hengduan Mountains, western China. Results: We found that egg size, age at sexual maturity, and mean age increased with decreasing length of the growth season, whereas clutch size showed a converse cline. Body size did not increase with decreasing length of the growth season, but was tightly linked to lifetime activity (i.e. the estimated number of active days during lifetime). Males and females differed in their patterns of geographic variation in growth rates, which may be the result of forces shaping the trade-off between growth and reproduction in different environments. Conclusions: Our findings suggest that growth season plays an important role in shaping variation in life-history traits in B. andrewsi across geographical gradients

Origin of superconductivity in nominally "undoped" T'-La2−x_{2-x}Yx_{x}CuO4_{4} films

We have systematically studied the transport properties of the La$_{2-x}$Y$_{x}$CuO$_{4}$(LYCO) films of T'-phase ($0.05\leq x \leq 0.30$). In this nominally "undoped" system, superconductivity was acquired in certain Y doping range ($0.10\leq x \leq 0.20$). Measurements of resistivity, Hall coefficients in normal states and resistive critical field ($H^\rho_{c2}$)in superconducting states of the T'-LYCO films show the similar behavior as the known Ce-doped n-type cuprate superconductors, indicating the intrinsic electron-doping nature. The charge carriers are induced by oxygen deficiency. Non-superconducting Y-doped Pr- or Nd-based T'-phase cuprate films were also investigated for comparison, suggesting the crucial role of the radii of A-site cations in the origin of superconductivity in the nominally "undoped" cuptates. Based on a reasonable scenario in the microscopic reduction process, we put forward a self-consistent interpretation of these experimental observations.Comment: 8 pages, 9 figure

An inverse approach to determine complex modulus gradient of field-aged asphalt mixtures

This study develops a new mechanical-based method to determine the complex modulus and modulus gradient of field-aged asphalt mixtures using the direct tension test. Due to the non-uniform aging nature of the field cores, the mechanical responses must be measured at different depths. Meanwhile, the monotonic load is not applied at the neutral axis of the field core specimen due to the modulus gradient, the tensile part of the strain is used and should be separated from the measurement because of the eccentric loading. The modulus gradient parameters, the location of the neutral axis, and the stress distribution are first obtained using the elastic formulas for a series of loading times. Then the complex modulus is determined using the Laplace transform and the elastic–viscoelastic correspondence principle. An inverse approach and iteration are then proposed by using the pseudo strain to accurately calculate the modulus gradient parameters after the relaxation modulus and reference modulus are determined