A protocol for the combined sub-fractionation and delipidation of lipid-binding proteins by hydrophobic interaction chromatography

Cellular lipids frequently co-purify with lipid binding proteins isolated from tissue extracts or heterologous host systems and as such hinder in vitro ligand binding approaches for which the apo-protein is a prerequisite. Here we present a technique for the complete removal of unesterified fatty acids, phospholipids, steroids and other lipophilic ligands bound to soluble proteins, without protein denaturation. Peroxisome proliferator activated receptor gamma ligand binding domain and intracellular fatty acid binding proteins were expressed in an Escherichia coli host and completely delipidated by hydrophobic interaction chromatography using phenyl sepharose. The delipidation procedure operates at room temperature with complete removal of bound lipids in a single step, as ascertained by mass spectrometry analysis of organic solvent extracts from purified protein samples. The speed and capacity of this method makes it amenable to scale-up and high-throughput applications. The method can also easily be adapted for other lipid binding proteins that require delipidation under native conditions.

Visible transparent, UV-blocking polymer nanocomposite films containing nano-sized organic-LDH (Layered Double Hydroxide) hybrid

A nano-sized Mg2Al layered double hydroxide (LDH) was used for encapsulating an organic UV absorber, 2-hydroxy-4- methoxybenzeophenone-5-sulfonic acid (HMBS), to produce HMBS@LDH hybrid nano-platelets. Upon dispersing this organic-inorganic hybrid LDH into ethylene-vinyl alcohol copolymer (EVOH) for film casting, a thin polymer
nanocomposite film that is UV opaque but highly transparent to visible light (higher than 90%) was formed. Thermogravimetry (TG) analysis confirmed that the intercalation of HMBS into LDH considerably increased the thermal stability of HMBS. Such an improvement was attributed to the strong guest-host interaction between the HMBS anions and the LDH layers. Also, the nanocomposite films were flexible and had good mechanical properties.

Synthesis and structure of an ether-bridged double ladder compound: potential in host - guest chemistry

The synthesis of the first example of an organotin double ladder (6) containing a functional group within the spacer is reported. In the solid state, compound 6 shows an interlaminar cavity whose size and shape suggest the possibility of host–guest chemistry. ¹¹⁹Sn-NMR and ESMS show that compound 6 undergoes extensive dissociation in solution. ESMS of compound 6 to which have been added Li⁺, Na⁺, Mg²⁺ or Cu²⁺ show only minimal interaction.

Guest editors' introduction : Special issue on trust, security, and privacy in parallel and distributed systems

In modern computing paradigms, most computing systems, e.g., cluster computing, grid computing, cloud computing, the Internet, telecommunication networks, Cyber- Physical Systems (CPS), and Machine-to-Machine communication networks (M2M), are parallel and distributed systems. While providing improved expandability, manageability, efficiency, and reliability, parallel and distributed systems increase their security weaknesses to an unprecedented scale. As the system devices are widely connected, their vulnerabilities are shared by the entire system. Because tasks are allocated to, and information is exchanged among the system devices that may belong to different users, trust, security, and privacy issues have yet to be resolved. This special issue of the IEEE Transactions on Parallel and Distributed Systems (TPDS) highlights recent advances in trust, security, and privacy for emerging parallel and distributed systems. This special issue was initiated by Dr. Xu Li, Dr. Patrick McDaniel, Dr. Radha Poovendran, and Dr. Guojun Wang. Due to a large number of submissions, Dr. Zhenfu Cao, Dr. Keqiu Li, and Dr. Yang Xiang were later invited to the editorial team. Dr. Xu Li was responsible for coordinating the paper review process. In response to the call for papers, we received 150 effective submissions, out of which 24 are included in this special issue after rigorous review and careful revision, presenting an acceptance ratio of 16 percent. The accepted papers are divided into three groups, covering issues related to trust, security, and privacy, respectively.

Solid-state NMR as a probe of anion binding: molecular dynamics and associations in a [5]polynorbornane bisurea host complexed with terephthalate

A range of solid-state NMR techniques is used to characterise a molecular host:guest complex consisting of a [5]polynorbornane bisurea host binding a terephthalate dianion guest. Detailed information is obtained on the molecular dynamics and associations from the point of view of both the host and guest molecules. The formation of the complex in the solid state is confirmed using (1)H 2D exchange NMR, and the 180° flipping of the (2)H-labelled terephthalate guest and its eventual expulsion from the complex at elevated temperatures are quantified using variable-temperature (2)H spin-echo experiments. Two-dimensional (1)H-(13)C HETCOR spectra obtained under fast magic angle spinning conditions (60 kHz) show a high resolution despite the poor crystallinity of the solid complex, and clearly reveal changes in the rigidity of the host molecule when complexed. Short-range intra- and intermolecular (1)H-(1)H proximities are also detected using 2D SQ-DQ correlation methods, providing insight into the molecular packing in the solid phase.

Positivism: one ring to rule them all? A tale of information systems research methodology

The tale of research methodology in information systems is told through the fantasy of Tolkien’s Lord of the Rings. The tale is intended to be at once a piece of light hearted fun in its placement of the struggles of research methodology as an epic story but, in the tradition of the court jester, attempts to provide a new perspective on Information Systems (IS) research methodology and our struggles with positivism in particular. Our tale is one of developing a greater maturity and confidence in IS methodology and introduces postmodern methodologies to Information Systems. Our tale, our pastiche, is itself postmodern.

Guest editorial: foreword to the special issue on aggregation operators

The fourteen papers in this special section are devoted to aggregation operators with respect to knowledge based systems.

Gambling and corporate social responsibility (CSR) : re-defining industry and state roles on duty of care, host responsibility and risk management

During the 1990s, states embraced legalised gambling as a means of supplementing state revenue. But gaming machines (EGMs, pokies, VLTs, Slots) have become increasingly controversial in countries such as Australia, Canada and New Zealand, which experienced unprecedented roll-out of gaming machines in casino and community settings; alongside revenue windfalls for both governments and the gambling industry. Governments have recognised that gambling results in a range of social and economic harms and, similar to tobacco and alcohol, have introduced public policies predicated on harm minimisation. Yet despite these, gaming losses have continued to climb in most jurisdictions, along with concerns about gambling-related harms. The first part of this article discusses an emerging debate in Ontario Canada, that draws parallels between host responsibility in alcohol and gambling venues. In Canada, where government owns and operates the gaming industry, this debate prompts important questions on the role of the state, duty of care and regulation ‘in the public interest’ and on CSR, host responsibility and consumer protection. This prompts the question: Do governments owe a duty of care to gamblers?

The article then discusses three domains of accumulating research evidence to inform questions raised in the Ontario debate: evidence that visible behavioural indicators can be used with high confidence to identify problem gamblers on-site in venues as they gamble; new systems using player tracking and loyalty data that can provide management with high precision identification of problem gamblers and associated risk (for protective interventions); and research on technological design features of new generation gaming products in interaction with players, that shows how EGM machines can be the site for monitoring/protecting players. We then canvass some leading international jurisdictions on gambling policy CSR and consumer protection.

In light of this new research, we ask whether the risk of legal liability poses a tipping point for more interventionist public policy responses by both the state and industry. This includes a proactive role for the state in re-regulating the gambling industry/products; instituting new forms of gaming machine product control/protection; and reinforcing corporate social responsibility (CSR) and host responsibility obligations on gambling providers – beyond self-regulatory codes. We argue the ground is shifting, there is new evidence to inform public policy and government regulation and there are new pressures on gambling providers and regulators to avail themselves of the new technology – or risk litigation

Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans

Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host-pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (-25.3 ± 0.4) than their non-infected counterparts (-26.3±0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness.

Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant Ka was 1,639 M-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

Spectroscopic and computational characterizations of alkaline-earth- and heavy-metal-exchanged natrolites

Synchrotron infrared (IR) and micro-Raman spectra of natrolites containing alkaline-earth ions (Ca2+, Sr2+, and Ba2+) and heavy metals (Cd2+, Pb2+, and Ag+) as extra-framework cations (EFCs) were measured under ambient conditions. Complementing our previous spectroscopic investigations of natrolites with monovalent alkali metal (Li+, Na+, K+, Rb +, and Cs+) EFCs, we establish a correlation between the redshifts of the frequencies of the 4-ring and helical 8-ring units and the size of the EFCs in natrolite. Through ab initio calculations we have derived structural models of Ca2+- and Ag+-exchanged natrolites with hydrogen atoms, and found that the frequency shifts in the H - O - H bending mode and the differences in the O - H stretching vibration modes can be correlated with the orientations of the water molecules along the natrolite channel. Assuming that the members of a solid solution series behave as an ideal mixture, we will be able to use spectroscopy to probe compositions. Deviation from ideal behavior might indicate the occurrence of phase separation on various length scales. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.