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In this paper, discrete element method (DEM) is used to generate randomly stacked proppant layer, and the particle size distribution, Young's modulus and initial stacking of proppant are considered. Based on these discrete stacking structures, cyclic uniaxial compression tests (ucts) were carried out, and mechanical and seepage analysis of the proppant layer was carried out. Larger particle size and larger Young's modulus will make the equivalent elastic modulus of particle combination larger. The particle distribution has a certain effect on the permeability coefficient of the whole combination in given condition.

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Purpose: Elevated levels or increases in circulating tumor cells (CTC) portend poor prognosis in patients with epithelial cancers. Less is known about CTCs as surrogate endpoints or their use for predictive biomarker evaluation. This study investigated the utility of CTC enumeration and characterization using the CellSearch platform, as well as mutation detection in circulating tumor DNA (ctDNA), in patients with advanced non–small cell lung cancer (NSCLC).Experimental Design: Forty-one patients were enrolled in a single-arm phase II clinical trial of erlotinib and pertuzumab. Peripheral blood was analyzed for CTC enumeration, EGFR expression in CTCs, and detection of oncogenic mutations in CTCs and ctDNA. Changes in CTC levels were correlated with 2[18F]fluoro-2-deoxy-d-glucose–positron emission tomographic (FDG-PET) and computed tomographic (CT) imaging and survival endpoints.Results: CTCs were detected (≥1 CTC) at baseline in 78% of patients. Greater sensitivity for mutation detection was observed in ctDNA than in CTCs and detected mutations were strongly concordant with mutation status in matched tumor. Higher baseline CTC counts were associated with response to treatment by Response Evaluation Criteria in Solid Tumors (RECIST, P = 0.009) and decreased CTC counts upon treatment were associated with FDG-PET and RECIST response (P = 0.014 and P = 0.019) and longer progression-free survival (P = 0.050).Conclusion: These data provide evidence of a correlation between decreases in CTC counts and radiographic response by either FDG-PET or RECIST in patients with advanced NSCLC. These findings require prospective validation but suggest a potential role for using CTC decreases as an early indication of response to therapy and ctDNA for real-time assessment of mutation status from blood. Clin Cancer Res; 18(8); 2391–401. ©2012 AACR.

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Yongfang Zhang,1,* Di Wang,2,* Weiqun Liu,1 Yin Zhang,3 Lina Zhou,4 Hanhuan Yuan,5 Jiaming Yao,6 Ming Li7 1Department of Nursing, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 3The Party and Government Office, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 4Department of Publicity, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 5Infectious Disease Control and Disinfection Management Section, Shanghai Pudong New Area Center for Disease Control and Prevention, Fudan University Pudong Institute of Preventive Medicine, Shanghai, People’s Republic of China; 6Columbia University School of Nursing, New York, NY, USA; 7Dean’s Office, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming LiShanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, 1500 W Zhouyuan Road, Pudong New Area, Shanghai, 201318, People’s Republic of ChinaTel +86 2168135590 Ext. 6001Fax +86 21-68135715Email liming1070@126.comJiaming YaoColumbia University School of Nursing, 560 W 168th Street, New York, NY, 10032, USATel +1-6463391188Email jy2349@cumc.columbia.eduObjective: To implement epidemic prevention among entry personnel, Shanghai has launched a number of Medical Observation Sites (Observation Site) for which high expectations are set. Ours is one such Observation Site.Methods: As part of a novel project, we did not have any previous experience to use as reference. Despite some challenges, we achieved satisfactory outcomes by establishing a stepwise approach to inbound passenger management, including the division of the working area of the Observation Site, dynamic management of the rooms, closed-loop management of the isolated personnel.Results: As of May 14, 2020, a total of 42 Observation Sites were operational in Pudong New Area. The following are the detailed descriptions of our Temporary Medical Observation Site set up and work flow.Conclusion: Early screening of inbound passengers as well as prompt and dynamic management of information about passengers’ close contacts play an active role in preventing an influx of cases. As a pilot program, we have a model that is effective despite some limitations.Keywords: COVID-19, observation, pandemic, screening, airport, room

Hot dry rock, as a renewable and sustainable energy source, can alleviate resource shortages and environmental pollution. Based on data from the Qiabuqia geothermal field and an established thermal-hydrological-mechanical coupled mathematical model, a novel horizontally layered enhanced geothermal system (EGS) is proposed and compared with the conventional double vertical well EGS. Under the simulated conditions in this paper, the comprehensive heat recovery performance of the horizontally layered EGS is significantly better than that of the double vertical well EGS. Specifically, although the average production temperature of the double vertical well EGS is higher than that of the horizontally layered EGS in the attenuation stage, the heat power output of the horizontally layered EGS ranges from 6.10 MW to 12.25 MW, which is 1.36 to 1.67 times that of the double vertical well EGS. Additionally, the heat recovery rate of the horizontally layered EGS is 6.63% higher than that of the double vertical well EGS and is thus more economical. Finally, parametric analysis was performed to investigate the influence of the controllable parameters on heat recovery for the horizontally layered EGS. The heat power output and heat extraction ratio are proportional to the pressure difference and well spacing and inversely proportional to the injection fluid temperature. The thermal power output is most greatly influenced by the pressure difference, followed by the well spacing and injection fluid temperature. The effects of the pressure difference and well spacing on the heat recovery rate are almost the same, and the injection fluid temperature has no effect.

While intramuscular vaccination with HPV16 antigens has been shown to induce robust tumor-specific immune responses in the periphery, this has led to limited efficacy in the clinic. One potential explanation is the lack of sufficient infiltration of antigen-specific T cells into the tumor. The few T cells that make their way into the tumor are met with a plethora of negative signals that suppress their activity and abrogate local T cell expansion. To overcome this limitation of intramuscular cancer vaccines, we have developed an approach using in situ vaccination with a combination of immune modulators and tumor antigens, all encoded by mRNAs and delivered using nanoparticles. In this study, we show the superior efficacy and immunogenicity of a locally delivered mRNA cancer vaccine over that of an intramuscular HPV16 cancer vaccine. Both routes of administration result in robust induction of antigen-specific T cells, but local administration of mRNA-encoded antigens and immune modulators also resulted in enhanced infiltration of immune cells into the tumor, local Th1/M1 cytokine induction, and more-complete tumor clearance. Specifically, we found that the inclusion of the immunomodulators IL-12 and TNFSF14/LIGHT enabled tumor clearance in a murine tumor model. While tumors treated with mRNA-encoded HPV16 antigen alone induced robust systemic antigen-specific responses, minimal levels of local T cell expansion and infiltration, proinflammatory cytokine induction, and tumor control were observed. By contrast, tumors treated with mRNA-encoded HPV16 antigen, IL-12p70, and TNFSF14 completely cleared large established HPV16 expressing tumors with long-lasting recurrence free survival and immune memory. This observation was replicated in in a second murine tumor model, confirming the superior potency of locally delivered mRNA cancer vaccines in combination with immunomodulators. Consequently, we are developing a locally administrated mRNA therapy for the treatment of patients with cervical intraepithelial neoplasia (CIN). Citation Format: Weiqun Liu, Diane M. Da Silva, Edward E. Lemmens, Colin J. McKinlay, Sangeeta Nath, Meredith L. Leong, Samuel Deutsch, W. Martin Kast, Ole Audun W. Haabeth. Local delivery of mRNA immunotherapy encoding HPV16 antigen, IL-12, and LIGHT/TNFSF14 results in superior immunogenicity and tumor clearance in a murine model of HPV16-driven cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5163.

Many cancer immunotherapies require the strong activation of the T-cell mediated adaptive immune response to elicit their full anti-tumor potential. Antigen processing and presentation is a complex, multistep process that can be significantly enhanced via antigen modification, leading to better antigen-specific immune responses. Using mRNA, we can express exogenous antigens inside the cell and facilitate the subcellular localization of these antigens to enhance antigen processing and presentation. In this work, we introduced endolysosomal trafficking domains from CD1d molecules to drive subcellular localization of antigenic proteins to the late endosomes (LE) to enhance class I and class II antigen loading. CD1d are molecules that naturally traffic between the membrane and the late endosomes, where antigens are processed and loaded to both class II and class I molecules in a TAP-independent manner. We compared the immunogenicity of a novel endolysosomal trafficking domain, human CD1d, coupled to a chimeric HPV16 E6 and E7 (HPV16E6E7-hCD1d) antigen to antigen designs intended to be either a) secreted (Sec-HPV16E6E7), b) retained in the endoplasmic reticulum (ER) by an ER retention signal KDEL (HPV16E6E7-KDEL) or c) unmodified antigen sequence (HPV16E6E7). To ensure intracellular translation and expression, all antigens were encoded and delivered as mRNAs. The immunogenicity of each antigen design was assessed in HPV16 positive cervical intraepithelial neoplasia (CIN) donor derived PBMCs and healthy controls. Using confocal microscopy, we observed that the hCD1d trafficking domain directed the translated E6E7 protein into late endosomes, which was not observed for any of the other antigen designs. Importantly, antigen localization to late endosomes resulted in significantly improved immunogenicity in vitro as well as in vivo. We observed a consistent increase in numbers of activated antigen-specific T cells across multiple CIN donor PBMCs treated with HPV16E6E7-hCD1d compared to the other 3 designs, as measured by Interferon gamma secretion, surface marker expression, and T-cell proliferation. To assess the generalizability of this approach, we also compared immunogenicity in human donor PBMCs using the human cytomegalovirus antigen pp65, and observed similar results. Lastly, the immunogenicity of each antigen design was tested in vivo by intramuscular injection of nanoparticle formulated mRNAs in C56/Bl6 mice, and inclusion of the murine analogue (mCD1d) resulted in significantly increased generation of HPV16-specific T cell responses. Based on these findings, we are developing a novel mRNA-based cancer therapeutic that includes the addition of hCD1d trafficking domain in the HPV16-specific antigen component. Citation Format: Weiqun Liu, Daniel Fernandez, Colin J. McKinlay, Daniel O. Frimannsson, Meredith L. Leong, W. Martin Kast, Samuel Deutsch, Ole Audun W. Haabeth. Modification of mRNA-encoded HPV16 antigens to include endolysosomal trafficking domains drives cross-presentation and results in superior in vivo and ex vivo antigen-specific responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 690.

The approach of mechatronic switch appears to be a promising way of elaborating self-started synchronous switching circuits for piezoelectric energy harvesting. In order to replace electronic switches, the mechatronic switch has to overcome a critical challenge: how to trace the variable amplitude adaptively in different vibration situations while bringing less damping to the system dynamics as possible? In this article, an improved design of self-adaptive mechatronic switch is proposed by using the snubber structure of viscous materials in series with a low-frequency oscillator. The duplicated effects of the oscillator's slow responses and the relaxation process of the viscous materials bring the advantages of reducing switching phase mismatch and enhancing the performance with less parameter sensitivity. In addressing the damping doubts, energy current analysis is performed for different parameters. It reveals that the mechanical loss from the mechatronic switch can be controlled to a faint level. Superior performance of the proposed approach is confirmed in comparison with the standard circuit for weakly coupled cases.

With nonlinear systems extensively studied for applications in vibration isolation, energy harvesting, etc., most of the studies focused on the response of the nonlinear oscillator defined by some explicit equations, namely the typical oscillator. Rare studies or approaches are devoted to the non-typical nonlinear oscillator for which the stiffness profile is possible defined by an arbitrary curve without an explicit function. This paper proposes a novel design method for both typical and non-typical monostable hardening oscillators, especially for the latter one in order to achieve some arbitrarily specified response. The key idea is to construct a series of linear equivalent oscillators to reproduce the response of the nonlinear oscillator. A trial stiffness characteristic expression of the linear equivalent oscillators has been given as a function of several particular variables. It has been verified that the linear equivalent oscillators can obtain the response for some typical nonlinear oscillators. Moreover, the method can be also used in a reversed way to identify the stiffness characteristics from a given response for either typical or non-typical systems. In particular, this parameter identification feature can be utilized to design a customized oscillator with arbitrarily specified hardening response. By constructing the linear equivalent oscillators to reproduce the desired response, the linear equivalent stiffness expression can be determined, while the customized nonlinear stiffness characteristics can be obtained accordingly. Experiments on an elaborated example have validated effectiveness of the proposed method. It shows that the mapping method can be used to determine the proper stiffness characteristics for customized hardening response beyond the scope of typical nonlinear oscillators.

CO2sequestration in coal seam has proved to be an effective way for reducing air pollution caused by greenhouse gases. A study on the rules of fluid transfer and reliability of CO2storage during gas injection is necessary for the engineering application. However, the clarification of multifield coupling in long-term CO2sequestration is the difficulty to solve the aforementioned problem. Previous investigations on the coupled model for CO2storage in coal seam were not exactly comprehensive; for example, the multiphase flow in the fracture and the nonlinear behavior of gas diffusion were generally neglected. In this paper, a new multistage pore model of the coal matrix and the corresponding dynamic diffusion model were adopted. Meanwhile, the CO2-induced coal softening and the CO2-water two-phase flow in coal fracture were also taken into account. Subsequently, all the mentioned mechanisms and interactions were embedded into the coupled hydromechanical model, and this new fully coupled model was well verified by a set of experimental data. Additionally, through the model application for long-term CO2sequestration, we found that the stored CO2molecules are mainly in an adsorbed state at the early injection stage, while with the continuous injection of gas, the stored CO2molecules are mainly in a free state. Finally, the roles of multiphase flow and gas dynamic diffusion on fluid transfer and coal behavior were analyzed. The results showed that the impact of multiphase flow is principally embodied in the area adjacent to the injection well and the coal seam with lower initial water saturation is more reliable for CO2sequestration, while the impact of gas dynamic diffusion is principally embodied in the area far away from the injection well, and it is safer for CO2sequestration in coal seam with greater attenuation coefficient of CO2diffusion.

Tobacco mosaic virus (TMV) infection can causes serious damage to tobacco crops. To explore the approach of preventing TMV infection of plants, two tobacco cultivars with different resistances to TMV were used to analyze transcription profiling before and after TMV infection. The involvement of biological pathways differed between the tolerant variety (Yuyan8) and the susceptible variety (NC89). In particular, the plant–virus interaction pathway was rapidly activated in Yuyan8, and specific resistance genes were enriched. Liquid chromatography tandem mass spectrometry analysis detected large quantities of antiviral substances in the tolerant Yuyan8. A novel Nicotiana tabacum leucine-rich repeat receptor kinase (NtLRR-RLK) gene was identified as being methylated and this was verified using bisulfite sequencing. Transient expression of TMV-green fluorescent protein in pRNAi-NtLRR-RLK transgenic plants confirmed that NtLRR-RLK was important for susceptibility to TMV. The specific protein interaction map generated from our study revealed that levels of BIP1, E3 ubiquitin ligase, and LRR-RLK were significantly elevated, and all were represented at node positions in the protein interaction map. The same expression tendency of these proteins was also found in pRNAi-NtLRR-RLK transgenic plants at 24 h after TMV inoculation. These data suggested that specific genes in the infection process can activate the immune signal cascade through different resistance genes, and the integration of signal pathways could produce resistance to the virus. These results contribute to the overall understanding of the molecular basis of plant resistance to TMV and in the long term could identify new strategies for prevention and control virus infection.

Pore pressure variations owing to fluid injection-extraction from deep sedimentary basins can potentially trigger shear slipping along pre-existing faults. We use a coupled two-phase flow and geomechanical model to better understand the physical processes associated with simultaneous injection of $$\hbox {CO}_{2}$$ and production of $$\hbox {CH}_{4}$$ . The model considers permeability changes induced by deformation and slip-dependent friction of the sliding fault. The simulation results show that a sudden stress drop associated with fault reactivation occurs after 46 days of simultaneous fluid injection-extraction. The gas production rate instantaneously decreases as a result of the pressure drawdown applied at the wellbore and then approaches a relatively stable state that cumulatively produces coalbed methane of $$5.90 \times 10^{7}\,\hbox {kg}$$ . A sensitivity study shows that the arrangement of well operations affects the fault slip timing and corresponding sliding distance, as well as the cumulative gas production. Increasing production-injection or injection-production cycle number advances the timing of fault reactivation and reduces the maximum slip. More cycles result in higher peak production and hence promote the corresponding cumulative gas production, which significantly improves methane productivity efficiency. The results of this study demonstrate the importance of well operations on fault reactivation and cumulative methane production during $$\hbox {CO}_{2}$$ -enhanced coalbed methane recovery.

Combination therapy offers promising opportunities for treating advanced non-small cell lung cancer (NSCLC). Here, we established a chitosan-based nanocomplex CE7Q/CQ/S to deliver molecular-targeted drug erlotinib (Er), Survivin shRNA-expressing plasmid (SV), and photothermal agent heptamethine cyanine dye (Cy7) in one platform for simultaneous near-infrared (NIR) fluorescence imaging and triple-combination therapy of NSCLC bearing epidermal growth factor receptor (EGFR) mutations. The obtained CE7Q/CQ/S exhibited favorable photothermal effects, good DNA binding ability, and pH/NIR dual-responsive release behaviors. The conjugated Er could mediate specific delivery of Cy7 to EGFR-mutated NSCLC cells to enable targeted NIR fluorescence imaging and photothermal therapy (PTT). The in vitro and in vivo results showed that downregulation of Survivin expression and the photothermal effects could act synergistically with Er to induce satisfactory anticancer effects in either Er-sensitive or Er-resistant EGFR-mutated NSCLC cells. By integrating chemo/gene/photothermal therapies into one theranostic nanoplatform, CE7Q/CQ/S could significantly suppress EGFR-mutated NSCLC, indicating its potential use in treating NSCLC. STATEMENT OF SIGNIFICANCE: The development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved overall survival in patients with NSCLC driven by EGFR mutations. Unfortunately, the emergence of acquired resistance of EGFR-TKIs is almost inevitable after treatment. Here, we constructed a NIR/pH dual-responsive nanocomplex CE7Q/CQ/S based on chitosan which could integrate targeted near-infrared fluorescence imaging and chemo/gene/phototheramal tri-therapies together. We found that CE7Q/CQ/S possessed a promising outcome in fighting against EGFR-mutated NSCLC. The inhibition of Survivin expression and the application of photothermal therapy could act synergistically with erlotinib and reverse erlotinib resistance. The results of this work suggested that this chitosan-based combination therapeutic nanoplatform could be a promising candidate for NSCLC treatment.

Multiple piezoelectric power sources are used for extending the bandwidth or the multi-direction operation capability of the vibration harvesters. Typical rectifier configurations including parallel or series connection before a shared rectifier or one rectifier per source are usually used for regulating the multiple sources. The problem of charge cancelation arises for the shared rectifier configuration while diodes are too many for the configuration of one rectifier per source. In this article, improved rectifier design is proposed for multiple sources by introducing a common ground branch. The improved scalable rectifier design is capable of unifying more than one sources of different voltage polarity to power the load without charge cancelation, thus promising better performance than the aforementioned configurations. The power enhancement is verified through simulations and experiments with a maximum boost of 91.9% and the effective bandwidth is increased by 23.3% at least. In particular, the design has the advantage of cost saving by reducing the diodes to almost the half in comparison with the configuration of one rectifier per source.

Nonlinear systems are more attractive for the wide bandwidth in contrast to linear vibration energy harvesters. Most available generators belong to a certain type of nonlinear systems and the Duffing oscillator is a most popular kind. Once the system type is determined with a specific equation form, the performance optimization is limited in a certain range, generally related to the parameter study of the system within a given frame. In this paper, a novel generator is proposed by merging the stiffness curves of two different source generators through utilization of the nonlinear cantilever with a curve fixture. The special merged stiffness characteristics break the response limitation of the specific stiffness profile such as the Duffing equation and bring new benefits with the generator bandwidth further broadened by integrating the advantages of the source generator. In order to verify the stiffness-merging concept, two Duffing generators and a proposed generator with stiffness fitted from the former two are fabricated using the nonlinear cantilever with specially designed fixture curves. Experimental and numerical investigations reveal that the proposed generator with the merged stiffness has better performance than the generators with the typical stiffness characteristics of Duffing systems. The effectiveness of the stiffness-merging method is well demonstrated.

With the development of interface-rich composites, crack penetration/deflection at the interfaces have been the focus of considerable research studies. Because the F-criterion may imperceptibly enlarge the potential crack deflection range, a modification was made and related numerical analyses were then conducted. It was found that the modified F-criterion is as effective as the F-criterion and not affected by the fracture toughness ratio of mode II to mode I, when predicting the crack penetration direction. Furthermore, based on the modified F-criterion, the potential crack deflection range gradually shrinks, as the friction coefficient on crack surfaces and the fracture toughness ratio of mode II to mode I increase. However, as the surface pressure increases, the potential crack deflection range gradually broadens. In general, the result that is based on the modified F-criterion is no more than the one that is based on the F-criterion, when predicting the potential crack deflection range. Additionally, in accordance with the modified F-criterion, crack deflection caused by shear failure occurs only when the mode II fracture toughness is similar to the mode I fracture toughness. Otherwise, tensile failure is the exclusive reason for crack deflection.

The water-bearing capacity and abnormal water-bearing area of the coal seam floor of working face no. II 632 at the Hengyuan coal mine was investigated using the network parallel electrical method. Based on the limit equilibrium theory and Mohr–Coulomb yield criterion, we obtained a critical water pressure formula. Using fault DF137 as an example, we found that the abnormal water-bearing phenomena around the working face was related to nearby faults and that the water inrush was mainly due to faults being activated during mining. The pathway of water inrush under the coupled effects of stress induced by mining and the confined water pressure was modelled in Flac3D based on the fluid structure interaction (FSI) method. Considering the economics and operational convenience, grouting the working face floor was recommended to prevent an inrush. Based on a geophysical evaluation, the grouting effectively prevented a potential inrush.

It is a promising technology to effectively extract energy from the environmental vibrations. Recent studies have indicated that nonlinear generators can generally overcome many significant disadvantages of linear generators stemming from the narrow bandwidth and the low power density. Nevertheless, owing to multiple steady-state behaviors of the nonlinear system, high-energy orbits are coexisting with low-energy orbits on a major portion of the operating frequency range. Nothing but the large amplitudes of oscillations on the high-energy orbit can contribute significantly to energy harvesting, which cannot be achieved automatically. Thus, an systematic adjustment strategy is proposed by slow structural characteristics matching technique or extra energy impact technique or a combination of the two for the higher-energy orbit under variable vibration excitations. Following the analytical orbits obtained from the theory, it is experimentally verified that the buckled beam generator can generate two orders of magnitude larger power with the adjustment strategy compared to the original power. Moreover, the consumed energy is negligible and enough to get rid of the high power regulator. The studied adjustment strategy and results of this work can provide valuable guidelines for wider applications of nonlinear generators, especially under variable vibration excitations.

Investigating the diffusion law of slurry while grouting in fractured aquifer is of great significance to the safety in coal mining. In this paper, we comprehensively studied the slurry diffusion in the fractured aquifer, which was grouted through horizontal injection holes. A theoretical model of slurry diffusion in the inclined tubular fractures, as well as the relationship between the distance of slurry diffusion and the grouting time, was established. Then the influence of different factors on the distance of slurry diffusion was analyzed, including rheological coefficient, the fracture width, grouting pressure, the fracture dip angle, and the velocity of flowing water. Finally, sensitivity analysis on the distance of slurry diffusion for pseudoplastic fluid and expansive fluid along the flowing water direction was made and the results show that the sensitivity of each factor to the diffusion distance of the two fluids along the flowing water is different, rheological index is the very significant factor to the diffusion distance of pseudoplastic fluid. However, for the expansive slurry, the fracture width is the very significant factor to the diffusion distance of it.

Tobacco mosaic virus (TMV) infection can causes serious damage to tobacco crops. To explore the approach of preventing TMV infection of plants, two tobacco cultivars with different resistances to TMV were used to analyze transcription profiling before and after TMV infection. The involvement of biological pathways differed between the tolerant variety (Yuyan8) and the susceptible variety (NC89). In particular, the plant-virus interaction pathway was rapidly activated in Yuyan8, and specific resistance genes were enriched. Liquid chromatography tandem mass spectrometry analysis detected large quantities of antiviral substances in the tolerant Yuyan8. A novel