Activity and coke formation of nickel and nickel carbide in dry reforming: A deactivation scheme from density functional theory

Dry reforming is a promising reaction to utilise the greenhouse gases CO2 and CH4. Nickel-based catalysts are the most popular catalysts for the reaction, and the coke formation on the catalysts is the main obstacle to the commercialisation of dry reforming. In this study, the whole reaction network of dry reformation on both flat and stepped nickel catalysts (Ni(111) and Ni(211)) as well as nickel carbide (flat: Ni3C(001); stepped: Ni3C(111)) is investigated using density functional theory calculations. The overall reaction energy profiles in the free energy landscape are obtained, and kinetic analyses are utilised to evaluate the activity of the four surfaces. By careful examination of our results, we find the following regarding the activity: (i) flat surfaces are more active than stepped surfaces for the dry reforming and (ii) metallic nickel catalysts are more active than those of nickel carbide, and therefore, the phase transformation from nickel to nickel carbide will reduce the activity. With respect to the coke formation, the following is found: (i) the coke formation probability can be measured by the rate ratio of CH oxidation pathway to C oxidation pathway (r(CH)/r(C)) and the barrier of CO dissociation, (ii) on Ni(111), the coke is unlikely to form, and (iii) the coke formations on the stepped surfaces of both nickel and nickel carbide can readily occur. A deactivation scheme, using which experimental results can be rationalised, is proposed. 

Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella

The implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals, essential aspects of the innate immune response to infections. We examined whether the larva of the wax moth Galleria mellonella could be used as a host model to conceptually approximate Klebsiella pneumoniae-triggered pneumonia. We report that the G. mellonella model is capable of distinguishing between pathogenic and nonpathogenic Klebsiella strains. Moreover, K. pneumoniae infection of G. mellonella models some of the known features of Klebsiella-induced pneumonia, i.e., cell death associated with bacterial replication, avoidance of phagocytosis by phagocytes, and the attenuation of host defense responses, chiefly the production of antimicrobial factors. Similar to the case for the mouse pneumonia model, activation of innate responses improved G. mellonella survival against subsequent Klebsiella challenge. Virulence factors necessary in the mouse pneumonia model were also implicated in the Galleria model. We found that mutants lacking capsule polysaccharide, lipid A decorations, or the outer membrane proteins OmpA and OmpK36 were attenuated in Galleria. All mutants activated G. mellonella defensive responses. The Galleria model also allowed us to monitor Klebsiella gene expression. The expression levels of cps and the loci implicated in lipid A remodeling peaked during the first hours postinfection, in a PhoPQ- and PmrAB-governed process. Taken together, these results support the utility of G. mellonella as a surrogate host for assessing infections with K. pneumoniae.

The role of microneedles for drug and vaccine delivery

INTRODUCTION: Transdermal drug delivery offers a number of advantages for the patient, not only due to its non-invasive and convenient nature, but also due to factors such as avoidance of first-pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedles (MNs) can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below.

AREAS COVERED: MNs have been extensively investigated for drug and vaccine delivery. The different types of MN arrays and their delivery capabilities are discussed in terms of drugs, including biopharmaceutics and vaccines. Patient usage and effects on the skin are also considered.

EXPERT OPINION: MN research and development is now at the stage where commercialisation is a viable possibility. There are a number of long-term safety questions relating to patient usage which will need to be addressed moving forward. Regulatory guidance is awaited to direct the scale-up of the manufacturing process alongside provision of clearer patient instruction for safe and effective use of MN devices.

Bringing sounds into use: Thinking of sounds as materials and a sketch of auditory affordances

We live in a richly structured auditory environment. From the sounds of cars charging towards us on the street to the sounds of music filling a dancehall, sounds like these are generally seen as being instances of things we hear but can also be understood as opportunities for action. In some circumstances, the sound of a car approaching towards us can provide critical information for the avoidance of harm. In the context of a concert venue, sociocultural practices like music can equally afford coordinated activities of movement, such as dancing or music making. Despite how evident the behavioral effects of sound are in our everyday experience, they have been sparsely accounted for within the field of psychology. Instead, most theories of auditory perception have been more concerned with understanding how sounds are passively processed and represented or how they convey information of world, neglecting how this information can be used for anything. Here, we argue against these previous rationalizations, suggesting instead that information is instantiated through use and, therefore, is an emergent effect of a perceiver’s interaction with their environment. Drawing on theory from psychology, philosophy and anthropology, we contend that by thinking of sounds as materials, theorists and researchers alike can get to grips with the vast array of auditory affordances that we purposefully bring into use when interacting with the environment.

'Talk to me': a mixed methods study on preferred physician behaviours during end-of-life communication from the patient perspective

Background
Despite the recognized importance of end-of-life (EOL) communication between patients and physicians, the extent and quality of such communication is lacking.

Objective
We sought to understand patient perspectives on physician behaviours during EOL communication.

Design
In this mixed methods study, we conducted quantitative and qualitative strands and then merged data sets during a mixed methods analysis phase. In the quantitative strand, we used the quality of communication tool (QOC) to measure physician behaviours that predict global rating of satisfaction in EOL communication skills, while in the qualitative strand we conducted semi-structured interviews. During the mixed methods analysis, we compared and contrasted qualitative and quantitative data.

Setting and Participants
Seriously ill inpatients at three tertiary care hospitals in Canada.

Results
We found convergence between qualitative and quantitative strands: patients desire candid information from their physician and a sense of familiarity. The quantitative results (n = 132) suggest a paucity of certain EOL communication behaviours in this seriously ill population with a limited prognosis. The qualitative findings (n = 16) suggest that at times, physicians did not engage in EOL communication despite patient readiness, while sometimes this may represent an appropriate deferral after assessment of a patient's lack of readiness.

Conclusions
Avoidance of certain EOL topics may not always be a failure if it is a result of an assessment of lack of patient readiness. This has implications for future tool development: a measure could be built in to assess whether physician behaviours align with patient readiness.

Joining together or pushing apart? Building relations and exploring difference through shared education in Northern Ireland

In divided societies, the promotion of cross-cultural contact through the education system has been central to efforts to improve intergroup relations. This approach is informed by an understanding of the contact hypothesis, which suggests that positive contact with a member of a different group should contribute to improvements in attitudes towards the group as a whole. While a substantial body of research provides support for contact theory, critics have argued that its emphasis on harmonious encounters can result in the neglect of group differences and associated issues of conflict and discrimination during contact. The research discussed in this article explores this tension with reference to two shared education projects in Northern Ireland. Research data, gathered primarily through interviews with pupils, confirms that divisive issues are rarely addressed during contact and explores several influences on this: the nature of pupils’ relationships, the programme structure, and the prevailing social norms of avoidance.

Survival and behaviour of the earthworms Lumbricus rubellus and Dendrodrilus rubidus from arsenate-contaminated and non-contaminated sites

Two arsenic- and heavy metal-contaminated mine-spoil sites, at Carrock Fell, Cumbria and Devon Great Consols Mine, Devon, were found to support populations of the earthworms Lumbricus rubellus Hoffmeister and Dendrodrilus rubidus (Savigny). L. rubellus and D. rubidus collected from the Devon site and an uncontaminated site were kept for 28 days in uncontaminated soil and in soil containing sodium arsenate (494 mg As kg^-1). The state of the specimens was recorded every 7 days using a semi-quantitative assessment of earthworm health (condition index, C. I.). The C. I. remained high for all specimens except those of L. rubellus and D. rubidus from uncontaminated sites, which displayed 60 and 10% mortality, respectively. L. rubellus collected from the Carrock Fell site, and L. rubellus and D. rubidus from an uncontaminated site, burrowed as rapidly into soil containing up to 1235 mg As kg^-1 in the form of sodium arsenate as into uncontaminated soil when placed on the soil surface. When earthworms were allowed a choice between uncontaminated soil and soil contaminated with sodium arsenate in concentrations of up to 1235 mg As kg^-1, the threshold concentration for avoidance of contaminated soil was lower for L. rubellus and D. rubidus from uncontaminated soil than for specimens from contaminated soil. There was no significant effect of pH on soil discrimination. The LC₅₀ concentration of As for L. rubellus from Devon Great Consols was significantly higher (P < 0.001) than for L. rubellus from the uncontaminated site: 1510 and 96 mg As kg^-1, respectively. © 2001 Elsevier Science Ltd. All rights reserved.

Perceptions of therapist responses to shame disclosures by clients: A quasi-experimental investigation with non-clinical participants

Background
Therapist responses to initial shame disclosure in therapy have received little empirical attention.

Aim
This study explored different therapeutic responses to shame disclosures in terms of their perceived helpfulness. Responses ranged from complete withdrawal from the feeling (withdrawal) to completely tuning into it (non-withdrawal). Given the tendency of shame to evoke avoidance, participants higher on shame-proneness (as measured by The Experience of Shame Scale) were expected to perceive withdrawal responses to shame as more helpful than non-withdrawal responses.

Methodology
Fifty-five non-clinical participants were assessed for shame-proneness before viewing videos of mock therapy sessions showing clients either disclosing shame (two videos) or shock (control condition). Participants then rated the helpfulness of different therapist responses. The responses differed in the degree they allowed the client to withdraw from their emotions.

Results
High shame proneness was associated with rating withdrawal responses to shame as least helpful. Overall, neither the withdrawal response nor the non-withdrawal response were rated as particularly helpful. The therapeutic response which addressed management strategies when shame is initially experienced in therapy was deemed most helpful.

Conclusion
Despite the tendency to withdraw from shame feelings, this response is not deemed helpful in therapy.

Novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines, induce apoptosis in multi-drug-resistant cancer cells

PURPOSE: The development of multi-drug resistance (MDR) due to the expression of members of the ATP binding cassette (ABC) transporter family is a major obstacle in cancer treatment. The broad range of substrate specificities associated with these transporters leads to the efflux of many anti-cancer drugs from tumour cells. Therefore, the development of new chemotherapeutic agents that are not substrates of these transporters is important. We have recently demonstrated that some members of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds are microtubule-depolymerising agents that potently induce apoptosis in several cancer cell lines and impair growth of mouse breast tumours. The aim of this current study was to establish whether PBOXs were capable of inducing apoptosis in cancer cells expressing either P-glycoprotein or breast cancer resistance protein (BCRP), two of the main ABC transporters associated with MDR.

METHODS: We performed in vitro studies to assess the effects of PBOXs on cell proliferation, cell cycle and apoptosis in human cancer cell lines and their drug-resistant substrains expressing either P-glycoprotein or BCRP. In addition, we performed a preliminary molecular docking study to examine interactions between PBOXs and P-glycoprotein.

RESULTS: We established that three representative PBOXs, PBOX-6, -15 and -16 were capable of inducing apoptosis in drug-resistant HL60-MDR1 cells (expressing P-glycoprotein) and HL60-ABCG2 cells (expressing BCRP) with similar potencies as in parental human promyelocytic leukaemia HL60 cells. Likewise, resistance to PBOX-6 and -16 was not evident in P-glycoprotein-expressing A2780-ADR cells in comparison with parent human ovarian carcinoma A2780 cells. Finally, we deduced by molecular docking that PBOX-6 is not likely to form favourable interactions with the substrate binding site of P-glycoprotein.

CONCLUSION: Our results suggest that pro-apoptotic PBOX compounds may be potential candidates for the treatment of P-glycoprotein- or BCRP-associated MDR cancers.

High accuracy android malware detection using ensemble learning

With over 50 billion downloads and more than 1.3 million apps in Google’s official market, Android has continued to gain popularity amongst smartphone users worldwide. At the same time there has been a rise in malware targeting the platform, with more recent strains employing highly sophisticated detection avoidance techniques. As traditional signature based methods become less potent in detecting unknown malware, alternatives are needed for timely zero-day discovery. Thus this paper proposes an approach that utilizes ensemble learning for Android malware detection. It combines advantages of static analysis with the efficiency and performance of ensemble machine learning to improve Android malware detection accuracy. The machine learning models are built using a large repository of malware samples and benign apps from a leading antivirus vendor. Experimental results and analysis presented shows that the proposed method which uses a large feature space to leverage the power of ensemble learning is capable of 97.3 % to 99% detection accuracy with very low false positive rates.

The 4Cs of Disaster Partnering: Communication, Coordination, Cooperation and Collaboration

Public, nonprofit and private organisations respond to large-scale disasters domestically and overseas. Critics of these assistance efforts, as well as those involved, often cite poor interorganisational partnering as an obstacle to successful disaster response. Observers frequently call for ‘more’ and ‘better’ partnering. We found important qualitative distinctions existed within partnering behaviours. We identified four different types of interorganisational partnering activities often referred to interchangeably: communication, cooperation, coordination and collaboration—the Four Cs. We derived definitions of the Four Cs from the partnering literature. We then tested them in a case study of the response to the 2010 Haiti earthquake. We suggest that the Four Cs are distinct activities, that organisations are typically strong or weak in one or more for various reasons, and that the four terms represent a continuum of increased interorganisational embeddedness in partnering activities.

Molecular markers in the treatment of metastatic colorectal cancer

Although significant progress has been made in colorectal cancer (CRC) treatment within the last decade with the approval of multiple new agents, the prognosis for patients with metastatic CRC remains poor with 5-year survival rates of approximately 8%. Resistance to chemotherapy remains a major obstacle in effective CRC treatment and many patients do not receive any clinical benefit from chemotherapy. In addition, other patients will experience adverse reactions to treatment resulting in dose modifications or treatment withdrawal, which can severely reduce treatment efficacy. Currently, significant research efforts are attempting to identify reliable and validated biomarkers with which will guide clinicians to make more informed treatment decisions. Specifically, the use of molecular profiling has the potential to assist the clinician in administering the correct drug, dose, or intervention for the patient before the onset of therapy thereby selecting a treatment strategy likely to have the greatest clinical outcome while minimizing adverse events. However, until recently, personalized medicine is a paradigm that has existed more in conceptual terms than in reality with very few validated biomarkers used routinely in metastatic CRC treatment. Rapid advances in genomic, transcriptomic and proteomic technologies continues to improve our understanding of tumor biology, but the search for reliable biomarkers has turned out to be more challenging than previously anticipated with significant disparity in published literature and limited translation into routine clinical practice. Recent progress with the identification and validation of biomarkers to the anti-epidermal growth factor receptor monoclonal antibodies including KRAS and possibly BRAF provide optimism that the goal of individualized treatment is within reach. This review will highlight and discuss current progress in the search for biomarkers, the challenges this emerging field presents, and the future role of biomarkers in advancing CRC treatment.

Liquids with permanent porosity

Porous solids such as zeolites and metal-organic frameworks are useful in molecular separation and in catalysis, but their solid nature can impose limitations. For example, liquid solvents, rather than porous solids, are the most mature technology for post-combustion capture of carbon dioxide because liquid circulation systems are more easily retrofitted to existing plants. Solid porous adsorbents offer major benefits, such as lower energy penalties in adsorption-desorption cycles, but they are difficult to implement in conventional flow processes. Materials that combine the properties of fluidity and permanent porosity could therefore offer technological advantages, but permanent porosity is not associated with conventional liquids. Here we report free-flowing liquids whose bulk properties are determined by their permanent porosity. To achieve this, we designed cage molecules that provide a well-defined pore space and that are highly soluble in solvents whose molecules are too large to enter the pores. The concentration of unoccupied cages can thus be around 500 times greater than in other molecular solutions that contain cavities, resulting in a marked change in bulk properties, such as an eightfold increase in the solubility of methane gas. Our results provide the basis for development of a new class of functional porous materials for chemical processes, and we present a one-step, multigram scale-up route for highly soluble 'scrambled' porous cages prepared from a mixture of commercially available reagents. The unifying design principle for these materials is the avoidance of functional groups that can penetrate into the molecular cage cavities.

Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development

Transdermal drug delivery offers a number of advantages for the patient, due not only its non-invasive and convenient nature, but also factors such as avoidance of first pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedle arrays can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below. Microneedles have been extensively investigated in recent decades for drug and vaccine delivery as well as minimally invasive patient monitoring/diagnosis. This review focuses on a range of critically important aspects of microneedle technology, namely their material composition, manufacturing techniques, methods of evaluation and commercial translation to the clinic for patient benefit and economic return. Microneedle research and development is finally now at the stage where commercialisation is a realistic possibility. However, progress is still required in the areas of scaled-up manufacture and regulatory approval.

Autonomous COLREGs Compliant Ship Navigation, Using BridgeSimulators and an Unmanned Vessel

This paper presents an approach to COLREGs compliant ship navigation. A system architecture is proposed, which will be implemented and tested on two platforms: networked bridge simulators and at sea trials using an autonomous unmanned surface vessel. Attention is paid to collision avoidance software and its risk mitigation.