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Viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. Due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. Here, we use coherent brightfield (COBRI) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. By detecting intrinsic scattered light via imaging-based interferometry, COBRI microscopy allows us to track the motion of a single vaccinia virus particle with nanometer spatial precision (<3 nm) in 3D and microsecond temporal resolution (up to 100,000 frames per second). We explore the possibility of differentiating the virus signal from cell background based on their distinct spatial and temporal behaviors via digital image processing. Through image postprocessing, relatively stationary background scattering of cellular structures is effectively removed, generating a background-free image of the diffusive virus particle for precise localization. Using our method, we unveil single virus particles exploring cell plasma membranes after attachment. We found that immediately after attaching to the membrane (within a second), the virus particle is locally confined within hundreds of nanometers where the virus particle diffuses laterally with a very high diffusion coefficient (∼1 μm/s) at microsecond time scales. Ultrahigh-speed scattering-based optical imaging may provide opportunities for resolving rapid virus-receptor interactions with nanometer clarity.

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This paper presents the results of numerical simulation of dry, forward combustion tube experiments. The kinetic aspects of in-situ combustion processes also are discussed. The goals of the study are to investigate processes also are discussed. The goals of the study are to investigate the fuel deposition mechanism and to identify the key parameters affecting the performance of in-situ combustion processes. The thermal simulator developed at Gulf R and D Co. was used in the study. It was modified to include the capillary outlet effects for a more realistic description of the oil and water productions. The following experimental data were matched: cumulative water and oil productions, position of the combustion front as a function of time, fuel consumption, position of the combustion front as a function of time, fuel consumption, temperature as a function of time and position, and the pressure drop across the tube. History matches were performed for two crude oils with distinctly different physical properties (gravities of 26.5 and 13 API [0. 896 and 0. 979 g/cm3]). The agreements between experimental data and simulation results were excellent. Results indicate that the component equilibrium K-values and the kinetics of cracking reactions are the most important parameters affecting the fuel deposition, and that the fuel deposition mechanism, the fuel composition, and the locations and sizes of the transient zones depend on the crude oil and reservoir rock properties. Simulation results are always sensitive to the K-values of the light oil component but insensitive to the K-values of the heavy oil component. Results are sensitive to the kinetics of cracking reaction only if the cracking reaction is catalytic or the peak temperature and the fuel consumption are sufficiently high. Furthermore, the fuel available may or may not be solely in the form of coke. Our study suggests that further investigations of the catalytic effect of reservoir rocks and reaction kinetics of the cracking reaction are needed. Also, more than two crude oil components may be required to simulate the evaporation effect of crude oil accurately. Introduction In in-situ combustion processes, many physical changes as well as chemical reactions take place simultaneously or sequentially in the vicinity of the combustion front. It is generally believed that the combustion zone is preceded by a cracking or superheated steam zone, where coke is formed and preceded by a cracking or superheated steam zone, where coke is formed and deposited on the sand grains, and some lighter crude oil components evaporate and move forward with the flowing gas phase. The kinetics of combustion and cracking reactions in the combustion zone and the cracking zone has been discussed widely in the literature. The mechanisms of the physical changes and chemical reactions occurring around the combustion zone can be studied effectively through numerical simulation by using a thermal simulator. Although a number of numerical simulations of combustion tube experiments have been performed with different thermal simulators, no conclusions regarding the mechanism of fuel deposition can be drawn from these studies. The mentioned simulations either neglect the formation of coke from cracking reaction or use a high cracking rate so that no residual oil will be present in the combustion zone. The mechanism of fuel deposition is controlled by two important processes: the evaporation of crude oil components and the kinetics of the processes: the evaporation of crude oil components and the kinetics of the cracking reaction. These two processes determine how much fuel eventually will be burned and how much fuel will be in the form of coke. It has been reported, that low-temperature oxidation can have a significant effect on the fuel deposition and fuel characteristics. However, this reaction is important only when oxygen is available downstream of the combustion front. If oxygen is used completely in a combustion tube experiment, low-temperature oxidation will not play an important role in the fuel deposition mechanism. For a system with a high cracking reaction rate, it is likely that all of the crude oil in the cracking zone will be either evaporated or coked so that coke is the sole source of fuel. However, if the cracking rate is so low that only a portion of crude oil in the cracking zone is evaporated or coked, then some residual crude oil also will be burned in the combustion zone. This is supported strongly by the experimental data of Hildebrand who conducted a number of combustion tube experiments using clean, crushed Berea sandpacks with a variety of crude oils. SPEJ p. 657

BackgroundMultidrug resistance (MDR) is a major obstacle in breast cancer treatment. The predominant mechanism underlying MDR is an increase in the activity of adenosine triphosphate (ATP)-dependent drug efflux transporters. Sulbactam, a β-lactamase inhibitor, is generally combined with β-lactam antibiotics for treating bacterial infections. However, sulbactam alone can be used to treat Acinetobacter baumannii infections because it inhibits the expression of ATP-binding cassette (ABC) transporter proteins. This is the first study to report the effects of sulbactam on mammalian cells.MethodsWe used the breast cancer cell lines as a model system to determine whether sulbactam affects cancer cells. The cell viabilities in the present of doxorubicin with or without sulbactam were measured by MTT assay. Protein identities and the changes in protein expression levels in the cells after sulbactam and doxorubicin treatment were determined using LC–MS/MS. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to analyze the change in mRNA expression levels of ABC transporters after treatment of doxorubicin with or without sulbactam. The efflux of doxorubicin was measures by the doxorubicin efflux assay.ResultsMTT assay revealed that sulbactam enhanced the cytotoxicity of doxorubicin in breast cancer cells. The results of proteomics showed that ABC transporter proteins and proteins associated with the process of transcription and initiation of translation were reduced. The mRNA expression levels of ABC transporters were also decreased when treated with doxorubicin and sulbactam. The doxorubicin efflux assay showed that sulbactam treatment inhibited doxorubicin efflux.ConclusionsThe combination of sulbactam and doxorubicin enhances the cytotoxicity of doxorubicin in the breast cancer cells by inhibiting the expression of ABC transporter proteins and proteins associated with the process of transcription and initiation of translation, and blocking the efflux of doxorubicin. Co-treatment of doxorubicin and sulbactam can be used in breast cancer treatment to decrease the prescribed dose of doxorubicin to avoid the adverse effects of doxorubicin.