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Burlak C, Wang ZY, Chihara RK, Lutz AJ, Wang Y, Estrada JL, Tector AJ. Identification of human preformed antibody targets in GTKO pigs. Xenotransplantation 2012; 19: 92–101. © 2012 John Wiley & Sons A/S. Abstract: Background:  Human preformed antibodies continue to recognize porcine xenografts, despite the advent of α‐galactosyltransferase knockout (GTKO) pigs. This study examined the potential reactivity of human preformed IgG and IgM antibodies toward antigens in the GTKO pig liver. Methods:  Human serum was analyzed for the concentration of IgG, IgM, anti‐αgal antibody, anti‐non‐αgal antibody and cytotoxicity toward domestic and GTKO fibroblasts and liver sinusoidal endothelial cells (LSEC). We detected preformed antibodies in human serum directed toward GTKO pig liver cells and tissue samples using advanced proteomic techniques. The targets of preformed antibodies were identified by MALDI TOF TOF mass spectrometry and validated by confocal microscopy, immunoblot, and immunoprecipitation. Results:  Human serum used in this study contained 2.06 μg/ml IgG and 0.013 μg/ml IgM directed toward GTKO fibroblasts. Human IgG and IgM bound to GTKO LSEC in a dose‐dependent manner and were cytotoxic. We detected 357 protein spots recognized by human IgG and 233 by human IgM. Two hundred and nineteen proteins were common to both human IgG and IgM. Mass spectrometry identified numerous immunoreactive proteins, of which 19 were membrane proteins on liver cells. The most significant to this study were α‐enolase, CFTR, and E‐cadherin, which were abundant in GTKO pig tissues and expressed on the surface of GTKO LSEC. Human IgG captured α‐enolase, CFTR, and E‐cadherin by immunoprecipitation validating the proteomic identification. Conclusion:  These experiments indicate that several membrane antigens in GTKO pigs could be recognized directly by human IgG or IgM. Further studies on the contribution of these antigens to antibody‐mediated xenograft rejection are necessary.

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SIGNIFICANCE This study affirms the long-term safety and efficacy of scleral contact lens use in patients with keratoconus. PURPOSE This study aimed to evaluate the safety and efficacy of contemporary scleral contact lenses in the visual rehabilitation of the keratoconic population. METHODS A retrospective study of keratoconic subjects examined between 2013 and 2018 was conducted. Subjects were included regardless of age, sex, pre-existing morbidity, or scleral lens design. Only eyes fit successfully with scleral contact lenses for ≥1 year were included. Exclusion criteria were prior corneal surgery, dystrophy, degeneration, and trauma. RESULTS A total of 157 eyes of 86 subjects met the study criteria. The mean Keratoconus Severity Score at initial fitting was 3.6 ± 1.0. Lenses were gas-permeable and nonfenestrated, with a mean overall diameter of 15.8 ± 0.6 mm and 70.1% toric scleral periphery. Physiological adverse events occurred in 9.6% of eyes, including microbial keratitis (0.6%), phlyctenulosis (0.6%), corneal abrasion (1.3%), contact lens–induced acute red eye (1.3%), corneal infiltrative events (1.3%), pingueculitis (1.3%), and hydrops (3.2%). Lens-related adverse events were documented in 55.4% of eyes. Adverse events related to surface issues included poor wetting in 1.9%, handling in 3.8%, reservoir fogging in 7.0%, lens intolerance in 7.6%, deposit in 8.9%, and broken lenses in 26.1% of eyes. The most common management strategies involved refits (54.0% of interventions), patient reeducation (29.5%), medical treatment (5.5%), surgical referral (6.8%), adjustment to wear time (2.5%), surface treatment (1.2%), and lens replacement (0.6%). Best-corrected distance logMAR visual acuity improved significantly from a mean of 0.50 in spectacles to a mean of 0.08 in scleral lenses ( P < .0001). During the study period, 14.6% of eyes lost best-corrected scleral lens visual acuity, all from keratoconus progression. CONCLUSIONS Consistent with other groups, our study demonstrates excellent safety and efficacy of scleral contact lenses in subjects with keratoconus.

Infrastructure is the lifeline for fulfilling most of the basic needs that support the well-being and prosperity of human society. To sustain improvements in quality of life, China, as a developing economy, needs more and better infrastructure, despite facing massive funding shortages. An enormous amount of its private capital is locked up because of the many obstacles to private investment. This study introduces a blockchain-based financing instrument for unlocking massive private capital to fund infrastructure projects in China. It draws on a literature review and expert survey to identify the major holdups preventing private capital from funding infrastructure projects and to compare the existing instruments used in infrastructure financing. A fuzzy AHP-SWOT analysis is conducted to reveal the main internal factors (strengths and weaknesses) and external factors (opportunities and threats) in using blockchain-based finance in infrastructure projects. Finally, a conceptual framework for a blockchain-based infrastructure financing system is formulated to take advantage of the strength and opportunities, meanwhile, counter the weakness and threats, and the framework is also validated through its deployment on Hyperledger Fabric.

Branching structure is often used as a supporting structure of the grid shell due to its geometrical and force-transferring features, and the rationality of its shape is very important. The “physical” and “numerical” hanging models can be used for the joint form-finding of the branching structure and free-form grid shell. However, slack elements may exist in the equilibrium model which corresponds to the inefficient members in the form-found branching structure. To solve this problem, a form-finding method of branching structure based on dynamic relaxation is proposed in this study. The proposed method clusters the elements of the branching model and equalizes the axial forces of the elements in the same cluster, in other words, there are no slack elements in the equilibrium branching model. This method overcomes the defect that the equilibrium branching model may have slack elements and needs many manual adjustments during the procedure of determining the rational shape of a branching structure, and effectively prevents the inefficient members existing in the form-found structure. Numerical examples are provided to demonstrate the characteristics of the proposed method and its effectiveness is verified as well.