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CD4+ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein beta-arrestin 1 positively regulated naive and activated CD4+ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through beta-arrestin 1-dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding beta-arrestin 1 (Arrb1) were much more resistant to experimental autoimmune encephalomyelitis, whereas overexpression of Arrb1 increased susceptibility to this disease. CD4+ T cells from patients with multiple sclerosis had much higher Arrb1 expression, and 'knockdown' of Arrb1 by RNA-mediated interference in those cells increased apoptosis induced by cytokine withdrawal. Our data demonstrate that beta-arrestin 1 is critical for CD4+ T cell survival and is a factor in susceptibility to autoimmunity.

Heavy-oil occurring in thick reservoir is an important resource world-wide. Heavy-oil recovery from such reservoir using cyclic steam is an efficient solution due to very high oil viscosity. However heavy oil recovery at later cyclic steam soaking is a real challenge, yet no direct analogues exists as an efficient solution. We proposed a new method called stereoscopic network development and needed for efficient heavy-oil recovery from thick reservoir, consisting of ten vertical wells and two horizontal wells in the following manner: 1. Stereoscopic network: adding two superposed horizontal wells between vertical wells in rectangular pattern. 2. Operation: steam injection through the upper horizontal well and production through the lower and all vertical wells. Field practices of managing a steam flood with stereoscopic network in thick reservoir has shown that oil production and oil-steam ratio increased obviously, and water cut decreased sharply. In this work, the field results obtained early and parameters were needed for field scale simulation. The numerical model has been developed by CMG simulation software and was validated with field data. Using field results and numerical simulations study on stereoscopic network development, the mechanism of stereoscopic network to enhanced heavy-oil recovery in thick reservoir has been studied theoretically and with field test results. And field scale simulations were performed to identify the efficiency of the new method and the optimal injection/production schemes. Specific conclusions as to how to apply the method in thick reservoir considering the effect of the method were reported.

The use of a vertical well pattern results in productivity deficiency and poor development effect when developing buried hill reservoirs with complex properties. In this work, experiments are conducted to determine the best pattern for complex structure wells in buried hill reservoirs. Discretization is employed in an experimental method that uses unit cubic rocks with a size of 5 cm × 5 cm × 5 cm. The rocks are bonded in a spotty or reticular design to form a macroscopic model. Based on water flooding similarity criteria of fractured reservoir, an experimental model similar to a quarter of a five-spot unit in an actual reservoir is designed and manufactured. By selectively plugging wells in the model, various well patterns are established. Simulation results indicate that the vertical–vertical well pattern exhibits the fastest water breakthrough, fastest increase in water cut, and lowest recovery under the same pressure difference and well spacing. The horizontal–horizontal well pattern has the slowest water cut increase and the highest final oil recovery. For fishbone wells, this pattern facilitates an ideal development effect when the percolation direction is perpendicular to the plane determined by the mother bore and branch. When liquid rate, water cut, and recovery are considered, the horizontal–horizontal well pattern is recommended when conditions allow.