Response of Mycobacterium smegmatis to the Cytochrome bcc Inhibitor Q203

For the design of next-generation tuberculosis chemotherapy, insight into bacterial defence against drugs is required. Currently, targeting respiration has attracted strong attention for combatting drug-resistant mycobacteria. Q203 (telacebec), an inhibitor of the cytochrome bcc complex in the mycobacterial respiratory chain, is currently evaluated in phase-2 clinical trials. Q203 has bacteriostatic activity against M. tuberculosis, which can be converted to bactericidal activity by concurrently inhibiting an alternative branch of the mycobacterial respiratory chain, cytochrome bd. In contrast, non-tuberculous mycobacteria, such as Mycobacterium smegmatis, show only very little sensitivity to Q203. In this report, we investigated factors that M. smegmatis employs to adapt to Q203 in the presence or absence of a functional cytochrome bd, especially regarding its terminal oxidases. In the presence of a functional cytochrome bd, M. smegmatis responds to Q203 by increasing the expression of cytochrome bcc as well as of cytochrome bd, whereas a M. smegmatis bd-KO strain adapted to Q203 by increasing the expression of cytochrome bcc. Interestingly, single-cell studies revealed cell-to-cell variability in drug adaptation. We also investigated the role of a putative second cytochrome bd isoform postulated for M. smegmatis. Although this putative isoform showed differential expression in response to Q203 in the M. smegmatis bd-KO strain, it did not display functional features similar to the characterised cytochrome bd variant.     

Interactions of Fullerene‐Polyglycerol Sulfates at Viral and Cellular Interfaces

Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water‐soluble fullerene‐polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV‐G) with baby hamster kidney cells serving as a model of host cell. Interference with L‐selectin‐ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)‐based inhibition assay and the leukocyte cell (NALM‐6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico‐ to nanomolar half maximal inhibitory concentrations (IC₅₀) are achieved. With their highly antiviral and anti‐inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.     

Dual thermo- and pH-responsive poly(N-isopropylacrylamide-co-(2-dimethylamino) ethyl methacrylate)-g-PEG nanoparticle system and its potential in controlled drug release

Polymer Bulletin - Stimulus-responsive nanoparticles have been widely used for many applications in biotechnology and medicine. In this study, dual thermo- and pH-responsive...     

Mammographic mass segmentation using multichannel and multiscale fully convolutional networks

Breast cancer is one of the leading causes of death among women worldwide. Mammographic mass segmentation is an important task in mammogram analysis. This process, however, poses a prominent challenge considering that masses can be obscured in images and appear with irregular shapes and low image contrast. In this study, a multichannel, multiscale fully convolutional network is proposed and evaluated for mass segmentation in mammograms. To reduce the impact of surrounding unrelated structures, preprocessed images with a salient mass appearance are obtained as the second input channel of the network. Furthermore, to jointly conduct fine boundary delineation and global mass localization, we incorporate more crucial context information by learning multiscale features from different resolution levels. The performance of our segmentation approach is compared with that of several traditional and deep-learning-based methods on the popular DDSM and INbreast datasets. The evaluation indices consist of the Dice similarity coefficient, area overlap measure, area undersegmentation measure, area oversegmentation measure, and Hausdorff distance. The mean values of the Dice similarity coefficient and Hausdorff distance of our proposed segmentation method are 0.915 ± 0.031 and 6.257 ± 3.380, respectively, on DDSM and 0.918 ± 0.038 and 2.572 ± 0.956, respectively, on INbreast, which are superior to those of the existing methods. The experimental results verify that our proposed multichannel, multiscale fully convolutional network can reliably segment masses in mammograms.     

CONSCOM: An OO Construction Scheduling and Change Management System

In a companion paper, an object-oriented (OO) information model was presented for construction scheduling, cost optimization, and change order management (CONSCOM), based on the creation of a domain-specific development framework. The framework architecture is developed using generic software design elements, called patterns, which provide effective low-level solutions for creating, organizing, and maintaining objects. The OO model has been implemented in a prototype software system for management of construction projects, called CONSCOM, using the Microsoft Foundation Class library in Visual C++. CONSCOM is particularly suitable for highway construction change order management. It can be used by the owner as an intelligent decision support system in schedule reviews, progress monitoring, and cost-time trade-off analysis for change order approval. The OO information model for construction scheduling cost management can be integrated into a concurrent engineering model for the architecture, engineering, and construction industry.     

Linear‐dendritic copolymers as nanocatalysts

Functionalized poly(ethylene glycol) (PEG) containing four chloride end functional groups (PEG‐Cl₄) was synthesized through reaction between cyanuric chloride and PEG‐(OH)₂. Chloride end functional groups of PEG‐Cl₄ were able to initiate the ring opening polymerization of 2‐ethyl‐2‐oxazoline and star copolymers containing a PEG core, and poly(2‐ethyl‐2‐oxazoline) (POX) arms were obtained. Polymerization was quenched using diethanolamine, and star copolymers containing hydroxyl end functional groups (PEG‐POX‐OH) were obtained. ε‐Caprolactone was then polymerized using the hydroxyl end functional groups of star copolymers and amphiphilic linear‐dendritic copolymers containing PEG and POX, and poly(caprolactone) (PCL) blocks were synthesized. Linear‐dendritic copolymers were able to load the organic and inorganic guest molecules. Application of host‐guest systems such as nanocatalyst for Heck chemical reaction was also investigated. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Riprap Effect on Hydraulic Fracturing Process of Cohesive and Non-cohesive Protective Levees

A comprehensive experimental study was conducted to evaluate the effects of soil properties and the rip-rap as well as cohesive and non-cohesive soil material and the riprap particle size on the breaching process and the failure mechanism of the levee. The results showed the crucial role of the riprap coverage and the soil properties in the breaching of the protective levees. In this regard, breaching was developed in both vertical and transverse directions. In the levee without riprap coverage, breach development was observed in the transverse direction while the levee was eroded in the streamwise direction. In contrast, in the levee with riprap coverage, breach development mainly occurred in the vertical direction. Furthermore, the flow rate across the breach was higher in the tests with no riprap compared to those with the riprap coverage. Comparisons suggested that the shorter the failure time, the longer the equilibrium time. The present research has some major implications for coastal and hydraulic engineering designs since the construction of levees is of great importance. Furthermore, the findings can be used to predict flooding and erosion induced by the embankment failure.

     

Electrosynthesis and physioelectrochemical properties of poly tyramine electroactive film in the presence of the surfactant: Comparable study

We describe in detail the advantages of a novel method of electrochemical preparation of poly tyramine (PT), based on the ability of anionic surfactants to form micelles in aqueous media. We demonstrate that the electropolymerisation process carried out in the presence of sodium dodecyl sulfate (SDS) at an oxidation potential lower than in an aqueous media yields better organized PT films. Theoretical calculations for tyramine (Ty) polymerization were carried out at density functional theory (DFT) level using the 6-31G(d,p) basis set. The improved physicochemical and structural properties of PT obtained in these conditions related to the electrocatalytic effect of SDS and change fractal dimension of the film. With respect to Ni-PT/G, Ni-SDS-PT/G electrode shows a higher catalytic performance for the electrocatalytic oxidation of methanol.     

Polymer-functionalized carbon nanotubes in cancer therapy: a review

The increasing importance of nanotechnology in the field of biomedical applications has encouraged the development of new nanomaterials endowed with multiple functions. Novel nanoscale drug delivery systems with diagnostic, imaging and therapeutic properties hold many promises for the treatment of different types of diseases, including cancer, infection and neurodegenerative syndromes. Carbon nanotubes (CNTs) are both low-dimensional sp² carbon nanomaterials exhibiting many unique physical and chemical properties that are interesting in a wide range of areas including nanomedicine. Since 2004, CNTs have been extensively explored as drug delivery carriers for the intracellular transport of chemotherapy drugs, proteins and genes. In vivo cancer treatment with CNTs has been demonstrated in animal experiments by several different groups. Herein, the recent works on anticancer drug delivery systems based on carbon nanotubes are reviewed and some of more specific and important novel drug delivery devices are discussed in detail. This paper focuses on modifications of CNTs by polymers through covalent and non-covalent attachments: two different methods as critical steps in preparation of anticancer drug delivery systems from CNTs. In this respect the in vivo and in vitro behaviors and toxicity of the CNTs modified by polymers are summarized as well. Well-functionalized CNTs did not show any significant toxicity after injection into mice. Moreover, administration and excretion of CNT-based nanocarriers are discussed. It was concluded that future development of CNT-based nanocarriers may bring novel opportunities to cancer diagnosis and therapy.