Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface.

Members of the epidermal growth factor receptor family (EGFR/ERBB1, ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are key targets for inhibition in cancer therapy. Critical for activation is the formation of an asymmetric dimer by the intracellular kinase domains, in which the carboxy-terminal lobe (C lobe) of one kinase domain induces an active conformation in the other. The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2 (refs 3-5). Crystal structures of complexes between the EGFR kinase domain and a fragment of MIG6 show that a approximately 25-residue epitope (segment 1) from MIG6 binds to the distal surface of the C lobe of the kinase domain. Biochemical and cell-based analyses confirm that this interaction contributes to EGFR inhibition by blocking the formation of the activating dimer interface. A longer MIG6 peptide that is extended C terminal to segment 1 has increased potency as an inhibitor of the activated EGFR kinase domain, while retaining a critical dependence on segment 1. We show that signalling by EGFR molecules that contain constitutively active kinase domains still requires formation of the asymmetric dimer, underscoring the importance of dimer interface blockage in MIG6-mediated inhibition

An exploration of the relationships between socioeconomics, land use and daily trip chain pattern among low-income residents

Daily trip chain complexity and type choices of low-income residents are examined based on activity travel diary survey data in Nanjing, China. Statistical tests reveal that non-work trip chain complexity is distinctly distinct between low-income residents and non-low-income residents. Low-income residents are inclined to make simple non-work chains. Two types of econometric models, a stereotype logit model and mixed logit model, are then developed to investigate the possible explanatory variables affecting their trip pattern. The number of stops within a chain and chain types are considered as dependent variables, while independent variables include household and personal characteristics as well as land use variables. Results show that once convenient and flexible conditions are supplied, low-income residents are more likely to make multiple activities in a trip chain. Areas with high population and employment densities are associated with complex work trip chains and more non-work activity involvement

Assessment of Severe Accident Depressurization Valve Activation Strategy for Chinese Improved 1000 MWe PWR

To prevent HPME and DCH, SADV is proposed to be added to the pressurizer for Chinese improved 1000 MWe PWR NPP with the reference of EPR design. Rapid depressurization capability is assessed using the mechanical analytical code. Three typical severe accident sequences of TMLB’, SBLOCA, and LOFW are selected. It shows that with activation of the SADV the RCS pressure is low enough to prevent HPME and DCH. Natural circulation at upper RPV and hot leg is considered for the rapid depressurization capacity analysis. The result shows that natural circulation phenomenon results in heat transfer from the core to the pipes in RCS which may cause the creep rupture of pipes in RCS and delays the severe accident progression. Different SADV valve areas are investigated to the influence of depressurization of RCS. Analysis shows that the introduction of SADV with right valve area will delay progression of core degradation to RPV failure. Valve area is to be optimized since smaller SADV area will reduce its effect and too large valve area will lead to excessive loss of water inventory in RCS and makes core degradation progression to RPV failure faster without additional core cooling water sources

Quality Control Method for a Micro-Nano-Channel Microfabricated Device

A variety of silicon-fabricated devices is used in medical applications such as drug and cell delivery, and DNA and protein separation and analysis. When a fluidic device inlet is connected to a compressed gas reservoir, and the outlet is at a lower pressure, a gas flow occurs through the membrane toward the outside. The method relies on the measurement of the gas pressure over the elapsed time inside the upstream and downstream environments. By knowing the volume of the upstream reservoir, the gas flow rate through the membrane over the pressure drop can be calculated. This quality control method consists of measuring the gas flow through a device and comparing the results with a standard curve, which can be obtained by testing standard devices. Standard devices can be selected through a variety of techniques, both destructive and nondestructive, such as SEM, AFM, and standard particle filtration

An overview on nonlinear porous flow in low permeability porous media

AbstractThis paper gives an overview on nonlinear porous flow in low permeability porous media, reveals the microscopic mechanisms of flows, and clarifies properties of porous flow fluids. It shows that, deviating from Darcy's linear law, the porous flow characteristics obey a nonlinear law in a low-permeability porous medium, and the viscosity of the porous flow fluid and the permeability values of water and oil are not constants. Based on these characters, a new porous flow model, which can better describe low permeability reservoir, is established. This model can describe various patterns of porous flow, as Darcy's linear law does. All the parameters involved in the model, having definite physical meanings, can be obtained directly from the experiments

Should bike sharing continue operating during the COVID-19 pandemic? Empirical findings from Nanjing, China

Coronavirus disease 2019 (COVID-19) has triggered a worldwide outbreak of pandemic, and transportation services have played a key role in coronavirus transmission. Although not crowded in a confined space like a bus or a metro car, bike sharing users will be exposed to the bike surface and take the transmission risk. During the COVID-19 pandemic, how to meet user demand and avoid virus spreading has become an important issue for bike sharing. Based on the trip data of bike sharing in Nanjing, China, this study analyzes the travel demand and operation management before and after the pandemic outbreak from the perspective of stations, users, and bikes. Semi-logarithmic difference-in-differences model, visualization methods, and statistic indexes are applied to explore the transportation service and risk prevention of bike sharing during the pandemic. The results show that pandemic control strategies sharply reduced user demand, and commuting trips decreased more significantly. Some stations around health and religious places become more important. Men and older adults are more dependent on bike sharing systems. Besides, the trip decrease reduces user contact and increases idle bikes. And a new concept of user distancing is proposed to avoid transmission risk and activate idle bikes. This study evaluates the role of shared micro-mobility during the COVID-19 pandemic, and also inspires the blocking of viral transmission within the city.Comment: 30 pages, 7 figures, 6 table