An infectious clone of enterovirus 71(EV71) that is capable of infecting neonatal immune competent mice without adaptive mutations

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD), which is a life threatening disease in certain children. The pathogenesis of EV71-caused HFMD is poorly defined due to the lack of simple and robust animal models with severe phenotypes that recapitulate symptoms observed in humans. Here, we generated the infectious clone of a clinical isolate from a severe HFMD patient. Virus rescued from the cDNA clone was infectious in cell lines. When administrated intraperitoneally to neonatal ICR, BALB/c and C57 immune competent mice at a dosage of1.4 × 104 pfu per mouse, the virus caused weight loss, paralysis and death in the infected mice after 4-5 days of infection. In the infected mice, detectable viral replication was detected in various tissues such as heart, liver, brain, lung, kidney, small intestine, leg skeletal muscle and medulla oblongata. The histology of the infected mice included massive myolysis, glomerular atrophy, villous blunting in small intestine, widened alveolar septum, diminished alveolar spaces and lymphocytes infiltration into the lung. By using the UV-inactivated virus as a control, we elucidated that the virus first amplified in the leg skeletal muscle tissue and the muscle tissue served as a primary viral replication site. In summary, we generated a stable EV71 infectious clone that is capable of infecting neonatal immune competent mice without adaptive mutations and provide a simple, valuable animal model for the studies of EV71pathogenesis and therapy.</p

Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy

During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaired respond to interferon-α (IFN-α) therapy. Transfection of the constructs encoding the three most dominant species of spliced variants into cells or ectopic expression of the two major spliced protein including HBSP and N-terminal-truncated viral polymerase protein result in strong suppression of IFN-α signaling transduction, while mutation of the major splicing-related sites of HBV attenuates the viral anti-IFN activities in both cell and mouse models. These results have associated the productions of HBV spliced variants with the failure response to IFN therapy and illuminate a novel mechanism where spliced viral products are employed to resist IFN-mediated host defense. </p

Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus

A new avian-origin influenza virus A (H7N9) recently crossed the species barrier and infected humans; therefore, there is an urgent need to establish mammalian animal models for studying the pathogenic mechanism of this strain and the immunological response. In this study, we attempted to develop mouse models of H7N9 infection because mice are traditionally the most convenient models for studying influenza viruses. We showed that the novel A (H7N9) virus isolated from a patient could infect inbred BALB/c and C57BL/6 mice as well as outbred Institute of Cancer Research (ICR) mice. The amount of bodyweight lost showed differences at 7 days post infection (d.p.i.) (BALB/c mice 30%, C57BL/6 and ICR mice approximately 20%), and the lung indexes were increased both at 3 d.p.i. and at 7 d.p.i.. Immunohistochemistry demonstrated the existence of the H7N9 viruses in the lungs of the infected mice, and these findings were verified by quantitative real-time polymerase chain reaction (RT-PCR) and 50% tissue culture infectious dose (TCID50) detection at 3 d.p.i. and 7 d.p.i.. Histopathological changes occurred in the infected lungs, including pulmonary interstitial inflammatory lesions, pulmonary oedema and haemorrhages. Furthermore, because the most clinically severe cases were in elderly patients, we analysed the H7N9 infections in both young and old ICR mice. The old ICR mice showed more severe infections with more bodyweight lost and a higher lung index than the young ICR mice. Compared with the young ICR mice, the old mice showed a delayed clearance of the H7N9 virus and higher inflammation in the lungs. Thus, old ICR mice could partially mimic the more severe illness in elderly patients. </p

AN ANALYSIS OF CARSHARING AND BATTERY ELECTRIC VEHICLES IN THE UNITED STATES

According to the California Air Resources Board (CARB, 2020), light-duty vehicles are responsible for 13 percent of statewide NOx emissions and 28 percent of statewide greenhouse gas emissions. Scientists, policymakers, and car manufacturers have been striving to reduce the air pollution and greenhouse gas emissions from the transportation sector using various measures, ranging from cleaner engines to alternatives to driving to reduce VMT. In this dissertation, I focus on a subset of these measures: carsharing programs and Battery Electric Vehicles (BEVs). In the first part of this dissertation, I explore the profile of households engaging in carsharing by estimating zero-inflated negative binomial (ZINB) models on data from the 2017 National Household Travel Survey (NHTS). My results show that households who are more likely to carshare are those who participate in other forms of sharing, have more Silent generation members, are less educated (the highest educational achievement is a high school degree), and have fewer vehicles than drivers. Conversely, households with more young adults (18 – 20 years old), with 2 or more adults and no children, take part in carsharing program less often. Moreover, households who took more part in ridesharing and have fewer vehicles than drivers are less likely to never carshare. Furthermore, households whose annual income between $75,000 and$150,000 are more likely to never carshare. In the second part of this dissertation, I concentrate on the adoption of BEVs. More specifically, I focus on two questions: 1) What are the characteristics of households who own battery electric vehicles (BEVs)?; and 2) Does the travel behavior of these households differ from the travel of households who have motor vehicles but not BEVs? To answer those questions, I characterize three groups of households based on their vehicle holdings: BEV-only, BEV+ (i.e., households with both one or more BEV and at least one conventional vehicle), and non-BEV households. I analyze data from the 2017 NHTS using mixed methods. Results show that BEV households are more likely to be Asian, well-educated, with a higher income and to live in higher population and employment density areas. Furthermore, BEV-only households are more likely to be composed of one adult (not retired) with fewer Baby Boomers. Yet, BEV+ households are more likely to be larger households with 2 or more adults. Also, BEV+ households are more likely to have more Generation X (37-52 years old in 2017) and Z members (20 years old or younger in 2017). They are also more likely to own their home. My analysis on gender (at the individual level) concluded that BEV owners are more likely to be men. Furthermore, I find that BEV households travel as much as non-BEV households. Although carsharing and BEVs could substantially decrease the environmental footprint of transportation, they are currently far from mainstream. To promote carsharing programs, their reach could be extended, they could be made more affordable, while increasing the cost of owning and operating private vehicles. Similarly, state and federal governments could continue to provide financial incentives to lower the purchase price difference between conventional and BE vehicles, manufacturers could provide extended warranties on batteries, and the charging infrastructure needs to be developed in order to attract more customers. The Covid-19 crisis is giving governments around the world an opportunity to invest in clean technologies to jumpstart the economy. It is critical to take advantage of this crisis to reduce air pollution and greenhouse gas emissions from transportation for the good of current and future generations

Research of Dielectric Breakdown Microfluidic Sampling Chip

Microfluidic chip is mainly driven electrically by external electrode and array electrode, but there are certain disadvantages in both of ways, which affect the promotion and application of microfluidic technology. This paper discusses a scheme that uses the conductive solution in a microchannel made by PDMS, replacing electrodes and the way of dielectric breakdown to achieve microfluidic chip driver. It could reduce the driving voltage and simplify the chip production process. To prove the feasibility of this method, we produced a microfluidic chip used in PDMS material with the lithography technology and experimented it. The results showed that using the dielectric breakdown to achieve microfluidic chip driver is feasible, and it has certain application prospect

The Optimization of Civil Aircraft Product Option Selection Considering the Economy Response with an Improved Non-Dominated Sorting Genetic Algorithm

To serve customized option selection for civil aircraft, a mathematical product option selection optimization model combined with an Improved Non-dominated Sorting Genetic Algorithm for decreasing aircraft fleet maintenance cost was investigated. For airlines, considering the economy and reliability in customized option selection is the most intuitive way to improve aircraft performance to generate the optimal formation configuration. Product option selection usually takes certain indicators as constraints (reliability and economy) to meet and maximize performance through equipment selection (the selected parameters include mean time between failures, price, etc.). To describe the customization needs of airlines by a mathematical model and find the optimal decision through an algorithm, a multi-objective, mathematical product option selection optimization model response with reliability parameters as a decision variable, maintainability as a link, and aircraft fleet maintenance and availability as an objective function is established to serve aircraft option selection in this paper. Next, the multi-objective genetic algorithm is used to solve the model, and the convergence, distribution and fitting accuracy of the objective functions are analyzed. Eventually, the landing gear system is used to verify the effectiveness of the model and method. After optimization, the aircraft fleet maintenance cost is reduced by 20.71%, and the availability is increased by 2.576%. Through the mathematical optimization model, the product configuration is provided for the development of the customization option selection project

Experimental Study on the Adhesion Strength of the Frozen Ice for Aircraft Moving Parts

At alpine regional airports, aircraft are covered with frozen ice when they encounter extreme weather such as heavy snow or frost. The movement parts of aircraft cabin doors, flaps and landing gear may be affected due to the infiltration of freezing ice, and the movement stagnation may occur when the the accumulation of ice is more serious. This paper sets up a mechanical performance test of frozen ice for this engineering problem to provide data that is beneficial to the selection of the mechanism drive and the determination of ice-breaking loads. The test is conducted based on the standard tensile shear test. In order to overcome problems such as the poor icing effect of the traditional specimen or the easy damage of the specimen ice, we improved the structure of the specimen and the method of the test. According to the characteristics of growth of frozen ice, we introduced freezing time, type of water quality and adhesion materials as test variables. The results show that: the ice adhesion strength of frozen ice increases and then decreases (&minus;15 &#8728;C&sim;&minus;55 &#8728;C). At the ambient temperature of &minus;15 &#8728;C&sim;&minus;55 &#8728;C and freezing for 2 h&sim;6 h, the ice adhesion strength of aluminum alloy surface ranges from 0.009 MPa to 0.568 MPa, and that of frozen ice on a silicone rubber surface is 0.005 MPa&sim;0.147 MPa. The duration of freezing did not significantly affect the adhesion strength of frozen ice. Among the three water qualities, the frozen ice from distilled water has the greatest adhesion strength, the lake water is the most medium, and the sea water is the smallest. The results of this test can be widely used in the determination of the ice-breaking load of civil aircraft, amphibious aircraft, ships, and the design of anti-ice/de-icing systems

LRU Division of Civil Aircraft Based on Two-step Iterative Analytic Hierarchy Process

Reasonable line replaceable unit (LRU) division can effectively improve the maintenance efficiency of civil aircraft, avoid the phenomenon of aircraft parking, and ensure the safe and reliable operation of civil aircraft. Under the premise of considering the influence of various factors in the design stage and operation process of civil aircraft, the design and operation of civil aircraft are carried out, a method of LRU division, two-step iterative analytical hierarchy process (TSI-AHP), is proposed. Firstly, the influence of relevant factors in the design and operation stages on LRU division of civil aircraft is investigated. Secondly, the influence of various factors are comprehensive considered, and the lowest structures of product decomposed by their function are regarded as the study objects, and the TSI-AHP is applied to implement LRU division of civil aircraft. Finally, the landing gear system of ARJ21-700 aircraft is treated as an example to realize the LRU division using the method proposed. The results show that the LRU partition method based on TSI-AHP can effectively realize the LRU partition of landing gear system of ARJ21-700 aircraft. The LRU partition project in this paper is basically consistent with the actual LRU project, which verifies the feasibility and effectiveness of this method, and provides a new idea for the LRU partition of domestic civil aircraft

IMPACT ANALYSIS OF BOLT-CLAMPING FORCE TO FILLED-HOLE LAMINATES INTERLAMINAR STRESS

Using composite laminates with a bolt-filled hole were proposed to study interlaminar stress distribution of laminates joints hole-edge,and a 3D finite element model with a zero-thickness cohesive element was established for solving holeedge interlaminar stress of laminated plate in tension.The results show that interlaminar normal stress distribution along the hole mainly affected by the bolt-clamping force,under the same bolt-clamping force,interlaminar normal stress value ranges is close;The interlaminar shear stress impact both by the bolt-clamping force and interface ply parameters,such as interlaminar shear stress of [-45 /90] and [0 /-45] interface is larger than others; Interlaminar normal stress caused by bolt-clamping force was mainly compressive stress,and it is beneficial for the interlaminar strength,but interlaminar shear stress generated in the same time is not help to improve the interlaminar strength,therefore,a reasonable clamping force can enhance the interlaminar strength for bolt composite joints

Experimental Study on the Adhesion Strength of the Frozen Ice for Aircraft Moving Parts

At alpine regional airports, aircraft are covered with frozen ice when they encounter extreme weather such as heavy snow or frost. The movement parts of aircraft cabin doors, flaps and landing gear may be affected due to the infiltration of freezing ice, and the movement stagnation may occur when the the accumulation of ice is more serious. This paper sets up a mechanical performance test of frozen ice for this engineering problem to provide data that is beneficial to the selection of the mechanism drive and the determination of ice-breaking loads. The test is conducted based on the standard tensile shear test. In order to overcome problems such as the poor icing effect of the traditional specimen or the easy damage of the specimen ice, we improved the structure of the specimen and the method of the test. According to the characteristics of growth of frozen ice, we introduced freezing time, type of water quality and adhesion materials as test variables. The results show that: the ice adhesion strength of frozen ice increases and then decreases (−15 ∘C∼−55 ∘C). At the ambient temperature of −15 ∘C∼−55 ∘C and freezing for 2 h∼6 h, the ice adhesion strength of aluminum alloy surface ranges from 0.009 MPa to 0.568 MPa, and that of frozen ice on a silicone rubber surface is 0.005 MPa∼0.147 MPa. The duration of freezing did not significantly affect the adhesion strength of frozen ice. Among the three water qualities, the frozen ice from distilled water has the greatest adhesion strength, the lake water is the most medium, and the sea water is the smallest. The results of this test can be widely used in the determination of the ice-breaking load of civil aircraft, amphibious aircraft, ships, and the design of anti-ice/de-icing systems