Identification and Phenotypic Plasticity of Metastatic Cells in a Mouse Model of Melanoma

Melanoma is the deadliest form of skin cancer due to its high propensity to metastasize and resistance to current therapies. We have created a spontaneous mouse model of metastatic melanoma (Dct-Grm1/K5-Edn3) where metastasis to the lungs is 80% penetrant. The primary tumors of these mice present cellular heterogeneity with cells at varying levels of differentiation. The main goal of this study was to determine the metastatic potential of the primary tumor resident Tyrosinase positive cells and evaluate the dynamic phenotypic changes as those cells move from the primary tumors to the sites of metastasis. To accomplish this aim I crossed the Dct-Grm1/K5-Edn3 mice to CreERT2/mT/mG mice to indelibly label Tyrosinase cell populations within the primary tumor with Green Fluorescent Protein (GFP) by topical application of 4-hydroxytamoxifen (4HT) at the tumor site. In vivo lineage tracing and characterization of GFP+ cells were performed in the metastatic lesions. In the 4HT treated Dct-Grm1/ K5-Edn3/Tyr-CreERT2/mT/mG mice, primary tumor derived Tyrosinase positive cells or their progeny (GFP+) established successful metastases in the distant organs indicating the tumorigenic capacity of the differentiated cell populations. Numerous metastatic melanoma cells were identified in the vasculature of the metastatic organs and established close association with the vascular endothelium. The intravascular cells lost pigmentation and did not express melanocytic markers; however, they mimicked endothelial cell properties and gained the expression of CD31 (also known as platelet endothelial cell adhesion molecule PECAM-1) and vascular endothelial (VE)-Cadherin. In the lung metastatic foci, GFP+ cells resumed pigmentation production and lost the expression of endothelial cell markers. Evidence from other metastatic organs in the mice further supported the phenotypic plasticity of metastatic melanoma cells. The in vivo lineage tracing system established in the melanoma mouse model revealed tumor phenotypic plasticity and will be a powerful model to evaluate and help us understand the etiology and pathogenesis of melanoma metastasis. Further characterization of those more aggressive cells in melanoma will allow for the development of new prognostic tests and novel therapeutic strategies to eliminate metastasis

Learning a Dilated Residual Network for SAR Image Despeckling

In this paper, to break the limit of the traditional linear models for synthetic aperture radar (SAR) image despeckling, we propose a novel deep learning approach by learning a non-linear end-to-end mapping between the noisy and clean SAR images with a dilated residual network (SAR-DRN). SAR-DRN is based on dilated convolutions, which can both enlarge the receptive field and maintain the filter size and layer depth with a lightweight structure. In addition, skip connections and residual learning strategy are added to the despeckling model to maintain the image details and reduce the vanishing gradient problem. Compared with the traditional despeckling methods, the proposed method shows superior performance over the state-of-the-art methods on both quantitative and visual assessments, especially for strong speckle noise.Comment: 18 pages, 13 figures, 7 table

Research on selectivity removing SO2 from flue gas with a novel absorbent

Compared with the traditional methods of removal SO2 from flue gas, the organic solvent absorption has some advantages as low investment, high SO2 absorption efficiency and desorption efficiency. For the industrial application of organic solvent absorption as soon as possible, some laboratory research on selectively removing SO2 and NOx from flue gas in the presence of CO2 and an enlarged experiment has been done with a novel absorbent of Mn(II)+ DMSO. The effect on desulfurization selectivity for absorbents is studied. And the regeneration capacities for absorbent are researched. The result shows that the novel absorbent has not only strong desulfurization efficiency, but also good selectivity for SO2 and CO2, the feasibility of desulfurization absorbent has been proved

Study on the Technology Conditions of Flue Gas Desulfurization with Organic Solvent

The technology experiment on Flue Gas Desulfurization (FDG) by DMSO method is studied in this paper, and the desulfurization efficiency is set out in various conditions. The results show that the desulfurization efficiency can be over 94% under the condition as follows: the rate of flow of DMSO=100 L/h, L/Gï¼40～50, absorbent concentration = 100 %DMSO, T=room temperature, the gas flow=60 ml∙min-1, inlet SO2 concentration= 0.1-0.5 %, the time of operation must be controlled in 30 minutes

Study on development of low-carbon building based on LCA

AbstractThis text did a research about the status of low-carbon technologies in building area, and discussed the necessity and importance of reducing carbon emissions in the full life cycle of building; constructed low-carbon assessment model of building; Explored the development of low carbon construction law field, and thus identified the difficulties and challenges faced in its development, finding effective ways and providing a theoretical basis for the healthy and rapid development of low-carbon buildings

Effects of drought stress on the seed germination and early seedling growth of the endemic desert plant Eremosparton songoricum (Fabaceae)

Eremosparton songoricum (Litv.) Vass. is an endemic and extremely drought-resistant desert plant with populations that are gradually declining due to the failure of sexual recruitment. The effects of drought stress on the seed germination and physiological characteristics of seeds and seedlings were investigated. The results showed that the germination percentage decreased with an increase of polyethylene glycol 6000 (PEG) concentration: -0.3 MPa (5 % PEG) had a promoting effect on seed germination, -0.9 MPa (15 % PEG)dramatically reduced germination, and -1.8 MPa (30 % PEG) was the threshold for E. songoricum germination. However, the contents of proline and soluble sugars and the activity of CAT increased with increasing PEG concentrations. At the young seedling stage, the proline content and CAT, SOD and POD activities all increased at 2 h and then decreased; except for a decrease at 2 h, the MDA content also increased compared to the control (0 h). These results indicated that 2 h may be a key response time point for E. songoricum to resist drought stress. The above results demonstrate that drought stress can suppress and delay the germination of E. songoricum and that the seeds accumulate osmolytes and augment the activity of antioxidative enzymes to cope with drought injury. E. songoricum seedlings are sensitive to water stress and can quickly respond to drought but cannot tolerate drought for an extended period. Although such physiological and biochemical changes are important strategies for E. songoricum to adapt to a drought-prone environment, they may be, at least partially, responsible for the failure of sexual reproduction under natural conditions

LIQUID-SOLID COUPLING RESPONSE OF SURROUNDING ROCK MASS OF LARGE-DIAMETER RIVER-CROSSING SHIELD TUNNEL

The purpose is to investigate the response of seepage field, displacement field and stress field in the surrounding rock mass during dynamic tunneling in soft soil area. Relied on a large-diameter river-crossing shield tunnel project, considering driving force, shield tail grouting pressure, and the friction resistance between the shield shell and the soil, a three-dimensional fine tunnel model considering the liquid-solid coupling effect in the soil during dynamic tunneling was established by employing the finite difference method. The response characteristics of pore water pressure, displacement and stress in the surrounding rock mass were obtained. The results show that during shield tunneling and shield tail grouting, the pore water pressure in the range of 0.5 times the hole diameter around the tunnel decreases and increases respectively due to the liquid-solid coupling in the surrounding rock mass. When the shield tunneling moves away, the pore water pressure of the soil near the vault decreases, and the pore water pressure near the tunnel arch bottom increases. The impact range of shield tail grouting on the vertical settlement of the upper soil is about 0.5 times the hole diameter. The shield tail grouting can effectively reduce the vertical settlement of the top soil and slow down the vertical uplift of the bottom soil. During shield tunneling the vertical stress distribution of the soil above the vault of the working position and around the excavation surface is funnel-shaped, and the vertical stress around the excavated tunnel decreases

Enhancement of cell membrane poration by the antimicrobial peptide Melp5

Melittin, a natural antimicrobial peptide comprising 26 amino acid residues, can kill bacteria by inducing pores in cell membranes. Clinical applications of melittin as an antibiotic require a thorough understanding of its poration mechanism and mutations that enhance its antimicrobial activity. Previous experiments showed Melp5, a variant of melittin with five mutations, exhibits a higher poration ability. However, the mechanism of the enhanced poration ability is not fully understood. Here, we investigated the mechanism by comparing the poration of melittin and Melp5 using coarse-grained (CG) and all-atom (AA) molecular dynamics (MD) simulations. We observe that Melp5 is likely to form a pore with 5 peptides (pentameric), while melittin is likely to form a pore with 4 peptides (tetrameric). Our atomistic MD simulations show that the pentameric pore of Melp5 has a higher water permeability than the tetrameric pore of melittin. We also analyze the stability of the pores of melittin and Melp5 by calculating the interaction energies of the pores. In particular, we investigate the effects of mutant residues on pore stability by calculating electrostatic and LJ interactions. These results should provide insights on the enhanced poration ability of Melp5 and push it toward applications

A preliminary study of in vitro and in vivo synergistic effects of ciprofloxacin and D-tyrosine against Pseudomonas aeruginosa isolates

Purpose: To investigate the synergistic antimicrobial effects of ciprofloxacin and D-tyrosine against drug-resistant bacteria.Method: The antimicrobial effects of ciprofloxacin and D-tyrosine on clinical isolates of multidrugresistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) no. 3556 were determined in vitro based on time-kill curve, and in vivo in P. aeruginosa-zebrafish infection model. Furthermore, 30 clinical isolates of multidrug-resistant P. aeruginosa were used in vitro to ascertain the synergistic effect of the two agents.Results: Combined use of ciprofloxacin and D-tyrosine produced synergistic effects against the clinical isolate of P. aeruginosa no. 3556 in vitro and in vivo. Synergism occurred in 96.67 % (95 % CI, range 83.33 - 99.41 %) of the clinical isolates, and ciprofloxacin dose was reduced in 90 % (95 % CI, range 74.38 - 96.54 %) of the clinical isolates in vitro.Conclusion: These preliminary results suggest that the combination of ciprofloxacin and D-tyrosine is a promising therapeutic strategy against MDR P. aeruginosa infections. Keywords: Ciprofloxacin, D-tyrosine, Synergistic, P. aeruginosa, Zebrafish infection model, Time-killing curv