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N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG-Fc contains a human sialo-complex type (hSCT) glycan of biantennary structure with two α2,6-sialylations and without core-fucosylation is an optimized glycoform developed to enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen but also in some cases provides gain-of-function effector activity. We used enzymatic glyco-engineering to prepare an IgG-Fc with homogeneous hSCT attached to each CH2 domain and solved its crystal structure. A compact form and an open form were observed in an asymmetric unit in the crystal. In the compact structure, the double glycan latches from the two hSCT chains stabilize the CH2 domains in a closed conformation. In the open structure, the terminal sialic acid (N-acetylneuraminic acid or NeuNAc) residue interacts through water-mediated hydrogen bonds with the D249-L251 helix, to modulate the pivot region of the CH2-CH3 interface. The double glycan latches and the sialic acid modulation may be mutually exclusive. This is the first crystal structure of glyco-engineered Fc with enhanced effector activities. This work provides insights into the relationship between the structural stability and effector functions affected by hSCT modification and the development of better antibodies for therapeutic applications.

The fluid flow and heat transfer characteristics of a free-surface liquid jet impingement cooling have been investigated numerically. The slot jet with water impinging normally on a flat plate is employed. To describe the turbulent structure, the turbulent governing equations are solved by a control-volume-based finite-difference method with a power-law scheme and the well-known turbulence model, which are associated with wall function. Numerical computations have been conducted with variations of jet exit Reynolds number (11,000 ≤ Re d ≤ 17,000), dimensionless jet-to-surface distance (3 ≤ H / d 0 ≤ 12), dimensionless jet width (1 ≤ B / d 0 ≤ 2), and the heat flux (140 kW/m 2 ≤ q ″ ≤ 280 kW/m 2 ). The theoretical model developed is validated by comparing the numerical predictions with available experimental data in the literature. Under the studied ranges, the variations of local Nusselt numbers by hydraulic diameter Nu d of the dimensionless jet-to-surface distance 3 ≤ H / d 0 ≤ 12 along the flat plate decrease monotonically from its maximum value at the stagnation point. In addition, the shape of the inlet area and jet-to-surface distance are optimized by using the response surface methodology (RSM) and the genetic algorithm (GA) method after solutions are carefully validated with available experimental results in the literature. Based on the optimal results, the optimum condition is in H / d 0 = 7.86 and B / d 0 = 2 for this physical model.

The turbulent fluid flow and heat transfer characteristics of air jet impingement onto the rotating and stationary heat sink have been investigated numerically and optimized using genetic algorithms (GAs). The squared heat sinks with uniform 5 × 5 pin–fins are employed. The turbulent governing equations are solved by using the finite volume method combined with the approaches of four different turbulent models based on the Reynolds-averaged Navier–Stokes (RANS). The relative performance of four turbulent models for predicting this type of flow and heat transfer is investigated by comparing the numerical results with available experimental data. It is found that the standard k–ɛ model can give predictions for better performance of fluid flow and heat transfer. Studied parameters are included the distance of nozzle to fin tip ( 0 ⩽ C / d ⩽ 11 ), Reynolds number ( 5019 ⩽ Re ⩽ 25 , 096 ) and rotational Reynolds number ( 0 ⩽ Re r ⩽ 8114 ) . It is found that Nu 0 ‾ increases with Re for a stationary heat sink. The effects of Re r on the average Nusselt number ( Nu Ω ‾ ) of a rotating heat sink with jet impingement demonstrate that heat transfer enhancement ( Nu Ω ‾ / Nu 0 ‾ ) is obvious in the case of smaller Re (Re = 5019), but Nu Ω ‾ / Nu 0 ‾ decreased with increasing Re. In addition, the optimization of this problem is also presented by using response surface methodology (RSM) and genetic algorithm (GA) method. Three design variables including the distance of nozzle to fin tip, fin height and fin width are selected for optimization. Based on the results, the optimum condition is C/d = 0, w / d = 0.77 and H f / d = 3.08 for a stationary and a rotating pin–fins heat sink.

A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.

Mice that lack IL-15 or the IL-15R α-chain (IL-15Rα) are deficient in peripheral CD8+, but not in CD4+, T cells. This CD8+ T cell-specific deficiency has now been investigated further by characterization of a new strain of IL-15Rα−/− mice. The adult mutant mice exhibited a specific reduction in the percentage of CD8-single positive TCRhigh thymocytes. The expression of Bcl-2 was reduced in both CD8+ thymocytes and naive T cells of the mutant animals, and the susceptibility of these cells to death was increased. Memory CD8+ cells were profoundly deficient in IL-15Rα−/−mice, and the residual memory-like CD8+ cells contained a high percentage of dead cells and failed to up-regulate Bcl-2 expression compared with naive CD8+ cells. Moreover, exogenous IL-15 both up-regulated the level of Bcl-2 in and reduced the death rate of wild-type and mutant CD8+ T cells activated in vitro. These results indicate that IL-15 and IL-15Rα regulate the expression of Bcl-2 in CD8+ T cells at all developmental stages. The reduced Bcl-2 content in CD8+ cells might result in survival defect and contribute to the reduction of CD8+ cells in IL-15Rα−/−mice.