PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers

Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG–polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide–alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.Novartis Institutes of Biomedical ResearchNational Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence Grant P30 CA14051)National Institutes of Health (U.S.) (Centers for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02)National Science Foundation (U.S.). Graduate Research FellowshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship

Microstructure, texture and tensile properties of ultrafine/nano grained magnesium alloy processed by accumulative back extrusion

An AZ31 wrought magnesium alloy was processed by employing multipass accumulative back extrusion process. The obtained microstructure, texture and room temperature tensile properties were characterized and discussed. Ultrafine grained microstructure including nano grains were developed, where the obtained mean grain size was decreased from 8 to 0.5 µm by applying consecutive passes. The frequency of both low angle and high angle boundaries increased after processing. Strength of the experimental alloy was decreased after processing, which was attributed to the obtained texture involving the major component lying inclined to the deformation axis. Both the uniform and post uniform elongations of the processed materials were increased after processing, where a total elongation of 68 pct was obtained after six-pass deformation. The contribution of different twinning and slip mechanism was described by calculating corresponding Schmid factors. The operation of prismatic slip was considered as the major deformation contributor. The significant increase in post uniform deformation of the processed material was discussed relying on the occurrence of grain boundary sliding associated with the operation of prismatic slip.Postprint (author's final draft

Organising and representing the poor in a clientelistic democracy: the decline of radical NGOs in Bangladesh

This paper examines the political role of radical development NGOs that emerged in Bangladesh to challenge the marginalization of subordinate groups and strengthen democratic processes. After briefly introducing the political context of Bangladesh and its NGOs, the paper identifies and defines a radical NGO sub-sector. It then reviews the activities of these organizations during the pre-1990 military government era and during the subsequent period of electoral democracy. Some important achievements are identified, but also many failures that have led to decline, leaving behind an NGO sector dominated by credit and service delivery organizations. The paper then explains this decline by focusing on three inter-related factors: (i) an institutional setting dominated by clientelistic structures that have undermined efforts to build horizontal alliances among excluded groups in civil society, or links between NGOs and political parties; (ii) a shift in donor support from mobilization to market-based service delivery agencies; and (iii) internal structures that have generated legitimacy and accountability problems by encouraging elite capture, co-option and personalised leadership in the radical sub-sector. It concludes with some brief reflections on the main implications of these failures

Through-thickness variations in recrystallization behavior in an Al-based ARB composite sheet

A composite sheet of commercially pure aluminum and an Al-0.3 wt.% Sc alloy (in the supersaturated solid solution condition) was produced by accumulative roll bonding at 200°C. The material was then subjected to isothermal annealing at 300°C for 1-30 minutes and cold water quenched. The transverse section was investigated by electron back-scatter diffraction (EBSD) to investigate the variations in microstructure and texture within Al layers through the sheet thickness. A faster spheroidization of the highly elongated lamellar band deformation structures was observed in the surface aluminum layer as compared to the mid- and quarter-thickness layers. In the quarter thickness aluminum layer so-called continuous recrystallization occurred and, thus, the p-fiber rolling texture was retained. Further growth in this layer led to secondary recrystallization of cube orientations. In contrast, in the surface aluminum layers the recrystallization and grain growth texture were relatively random. Intermediate behavior was observed in the mid-thickness aluminum layer. © Published under licence by IOP Publishing Ltd

On the complexities of microband interactions in a cold-deformed goss-oriented Ni single crystal

In this investigation, the three-dimensional nature of microband boundaries was investigated in a Goss-oriented Nickel single crystal. The sample was 30 pct deformed by plane strain compression and then characterized by several advanced techniques including three-dimensional electron backscatter diffraction (3D-EBSD) and transmission electron microscopy (TEM). In the longitudinal section of the sample, microbands were found to exhibit their classical strip-like appearance. However, the microband interfaces contain numerous curved features despite the average inclination of the interfaces closely matching the potential {111} slip planes. The microband boundary irregularities are argued to be the outcome of microband interactions, which are also linked to the orientation spread of deformation structures. Based on the detailed TEM investigation of the dislocation structures associated with intersecting microbands, it is argued that these interactions result in the disintegration and/or dissolution of microband boundary segments. A correlation between microband and cell boundaries was also found

Uncovering the true nature of deformation microstructures using 3D analysis methods

© Published under licence by IOP Publishing Ltd.Three-dimensional electron backscatter diffraction (3D EBSD) has emerged as a powerful technique for generating 3D crystallographic information in reasonably large volumes of a microstructure. The technique uses a focused ion beam (FIB) as a high precision serial sectioning device for generating consecutive ion milled surfaces of a material, with each milled surface subsequently mapped by EBSD. The successive EBSD maps are combined using a suitable post-processing method to generate a crystallographic volume of the microstructure. The first part of this paper shows the usefulness of 3D EBSD for understanding the origin of various structural features associated with the plastic deformation of metals. The second part describes a new method for automatically identifying the various types of low and high angle boundaries found in deformed and annealed metals, particularly those associated with grains exhibiting subtle and gradual variations in orientation. We have adapted a 2D image segmentation technique, fast multiscale clustering, to 3D EBSD data using a novel variance function to accommodate quaternion data. This adaptation is capable of segmenting based on subtle and gradual variation as well as on sharp boundaries within the data. We demonstrate the excellent capabilities of this technique with application to 3D EBSD data sets generated from a range of cold rolled and annealed metals described in the paper