On the mobility, membrane location and functionality of mechanosensitive channels in Escherichia coli

We thank Frans Bianchi and Franz Ho for assistance with molecular cloning, Tim Rasmussen for providing the pTRC-MscK plasmid, Andrew Robinson for providing the pBAD-mEos3.2 plasmid, Matthias Heinemann for assistance with the flow cytometry measurements, Paul Schavemaker for performing Smoldyn simulations and Michiel Punter for programming ImageJ plugins for PALM reconstructions and single-particle tracking. We thank Ian Booth for critical reading of the manuscript, and Christoffer Åberg and Matteo Gabba for valuable discussions. The authors would like to thank David Dryden and Marcel Reuter for performing preliminary experiments from which this work has been built. The work was funded by the EU FP7 ITN-network program NICHE.

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

We were supported by the Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Medical Research Council grants G0601498 and G1100546/2 (P.W.), Tenovus Scotland Grant G09/17 (A.J.M.) and the University of Aberdeen (P.W.). We thank O. Tüscher for discussion, P. Teismann and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment, L. Strachan, A. Plano, S. Deiana for help with behavioral testing.

Effects of allergic diseases and age on the composition of serum IgG glycome in children

Glycan analysis was partly supported by European Commission GlycoBioM (contract #259869), IBD-BIOM (contract #305479), HighGlycan (contract #278535), MIMOmics (contract #305280), HTP-GlycoMet (contract #324400) and IntegraLife (contract #315997) grants. The SEATON cohort was partly funded by the UK Medical Research Council (contract #80219) and Asthma UK (contract #00/011 and 02/017) grants.

Limits to sustained energy intake XXV : milk energy output and thermogenesis in Swiss mice lactating at thermoneutrality

Acknowledgements We are grateful to Ke-Xin Chen, Song Tan and Jing Cao (Wenzhou University) for care of the animals. We thank Dr. Teresa G. Valencak (Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna, Austria) for her assistance with the body temperature measurements using the thermo-sensitive passive transponders. We thank Peter Thomson (University of Aberdeen) for his technical assistance with the isotope analysis for the DLW measurements. This work was supported by grant (no. 31270458) from the National Natural Science Foundation of China, grant (pd2013374) from Zhejiang province, and grants (no. 14SK51A, 14SK52A) from Wenzhou University.

Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia

This work was supported by the grants from British Council China (Sino-UK higher Education for PhD studies) to Y.D. and C.D.M., and also from the following funding resources: Tenovus Scotland (G12/05, B.L.), The Carnegie Trust (RG13060-10, B.L.) and National Natural Science Foundation of China (91232724, Y.D.; 31100788, L.Z.; 81200933, N.N.S.; 31528011, B.L. and Y.D.).

See-saw relationship of the Holocene East Asian-Australian summer monsoon

D.E. and N.M. acknowledge support by the Leibniz Association (WGL) under Grant No. SAW-2013-IZW-2. F.H.M.’s research is funded through an Australian Postgraduate Award. I.O. is financially supported from TUBITAK under 2214/A program and by Ege University under the Research Project number 2015FEN028. This study received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie grant agreement No 691037. The publication of this article was funded by the Open Access Fund of the Leibniz Association. K.H.W. thank Rhawn F. Denniston for his wider involvement in the northwest Australian monsoon project and the Kimberley Foundation Australia for financial support for this project and Paul Wyrwoll for helpful comments. We are also grateful to Yanjun Cai for providing the Lake Qinghai record.

Essays in Empirical Operations Management: Bayesian Learning of Service Quality and Structural Estimation of Complementary Product Pricing and Inventory Management

This dissertation contributes to the rapidly growing empirical research area in the field of operations management. It contains two essays, tackling two different sets of operations management questions which are motivated by and built on field data sets from two very different industries --- air cargo logistics and retailing.

The first essay, based on the data set obtained from a world leading third-party logistics company, develops a novel and general Bayesian hierarchical learning framework for estimating customers' spillover learning, that is, customers' learning about the quality of a service (or product) from their previous experiences with similar yet not identical services. We then apply our model to the data set to study how customers' experiences from shipping on a particular route affect their future decisions about shipping not only on that route, but also on other routes serviced by the same logistics company. We find that customers indeed borrow experiences from similar but different services to update their quality beliefs that determine future purchase decisions. Also, service quality beliefs have a significant impact on their future purchasing decisions. Moreover, customers are risk averse; they are averse to not only experience variability but also belief uncertainty (i.e., customer's uncertainty about their beliefs). Finally, belief uncertainty affects customers' utilities more compared to experience variability.

The second essay is based on a data set obtained from a large Chinese supermarket chain, which contains sales as well as both wholesale and retail prices of un-packaged perishable vegetables. Recognizing the special characteristics of this particularly product category, we develop a structural estimation model in a discrete-continuous choice model framework. Building on this framework, we then study an optimization model for joint pricing and inventory management strategies of multiple products, which aims at improving the company's profit from direct sales and at the same time reducing food waste and thus improving social welfare.

Collectively, the studies in this dissertation provide useful modeling ideas, decision tools, insights, and guidance for firms to utilize vast sales and operations data to devise more effective business strategies.

Non-equilibrium induction of tin in germanium: towards direct bandgap Ge1-xSnx nanowires

The development of non-equilibrium group IV nanoscale alloys is critical to achieving new functionalities, such as the formation of a direct bandgap in a conventional indirect bandgap elemental semiconductor. Here, we describe the fabrication of uniform diameter, direct bandgap Ge1-xSnx alloy nanowires, with a Sn incorporation up to 9.2[thinsp]at.%, far in excess of the equilibrium solubility of Sn in bulk Ge, through a conventional catalytic bottom-up growth paradigm using noble metal and metal alloy catalysts. Metal alloy catalysts permitted a greater inclusion of Sn in Ge nanowires compared with conventional Au catalysts, when used during vapour-liquid-solid growth. The addition of an annealing step close to the Ge-Sn eutectic temperature (230[thinsp][deg]C) during cool-down, further facilitated the excessive dissolution of Sn in the nanowires. Sn was distributed throughout the Ge nanowire lattice with no metallic Sn segregation or precipitation at the surface or within the bulk of the nanowires. The non-equilibrium incorporation of Sn into the Ge nanowires can be understood in terms of a kinetic trapping model for impurity incorporation at the triple-phase boundary during growth.

Ultrahigh Purcell factor in low-threshold nanolaser based on asymmetric hybrid plasmonic cavity

A low-threshold nanolaser with all three dimensions at the subwavelength scale is proposed and investigated. The nanolaser is constructed based on an asymmetric hybrid plasmonic F-P cavity with Ag-coated end facets. Lasing characteristics are calculated using finite element method at the wavelength of 1550 nm. The results show that owing to the low modal loss, large modal confinement factor of the asymmetric plasmonic cavity structure, in conjunction with the high reflectivity of the Ag reflectors, a minimum threshold gain of 240 cm−1 is predicted. Furthermore, the Purcell factor as large as 2518 is obtained with optimized structure parameters to enhance rates of spontaneous and stimulated emission.

A systematic analysis of the role of GGDEF-EAL domain proteins in virulence and motility in Xanthomonas oryzae pv. oryzicola

The second messenger c-di-GMP is implicated in regulation of various aspects of the lifestyles and virulence of Gram-negative bacteria. Cyclic di-GMP is formed by diguanylate cyclases with a GGDEF domain and degraded by phosphodiesterases with either an EAL or HD-GYP domain. Proteins with tandem GGDEF-EAL domains occur in many bacteria, where they may be involved in c-di-GMP turnover or act as enzymatically-inactive c-di-GMP effectors. Here, we report a systematic study of the regulatory action of the eleven GGDEF-EAL proteins in Xanthomonas oryzae pv. oryzicola, an important rice pathogen causing bacterial leaf streak. Mutational analysis revealed that XOC_2335 and XOC_2393 positively regulate bacterial swimming motility, while XOC_2102, XOC_2393 and XOC_4190 negatively control sliding motility. The ΔXOC_2335/XOC_2393 mutant that had a higher intracellular c-di-GMP level than the wild type and the ΔXOC_4190 mutant exhibited reduced virulence to rice after pressure inoculation. In vitro purified XOC_4190 and XOC_2102 have little or no diguanylate cyclase or phosphodiesterase activity, which is consistent with unaltered c-di-GMP concentration in ΔXOC_4190. Nevertheless, both proteins can bind to c-di-GMP with high affinity, indicating a potential role as c-di-GMP effectors. Overall our findings advance understanding of c-di-GMP signaling and its links to virulence in an important rice pathogen.

Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.

Evaluation of semi-passive treatment technologies for septic lagoon capacity expansion

In Canada, increases in rural development has led to a growing need to effectively manage the resulting municipal and city sewage without the addition of significant cost- and energy- expending infrastructure. Storring Septic Service Limited is a family-owned, licensed wastewater treatment facility located in eastern Ontario. It makes use of a passive waste stabilization pond system to treat and dispose of waste and wastewater in an environmentally responsible manner. Storring Septic, like many other similar small-scale wastewater treatment facilities across Canada, has the potential to act as a sustainable eco-engineered facility that municipalities and service providers could utilize to manage and dispose of their wastewater. However, it is of concern that the substantial inclusion of third party material could be detrimental to the stability and robustness of the pond system. In order to augment the capacity of the current facility, and ensure it remains a self-sustaining system with the capacity to safely accept septage from other sewage haulers, it was hypothesized that pond effluent treatment could be further enhanced through the incorporation of one of three different technology solutions, which would allow the reduction of wastewater quality parameters below existing regulatory effluent discharge limits put in place by Ontario’s Ministry of the Environment and Climate Change (MOECC). Two of these solutions make use of biofilm technologies in order to enhance the removal of wastewater parameters of interest, and the third utilizes the natural water filtration capabilities of zebra mussels. Pilot-scale testing investigated the effects of each of these technologies on treatment performance under both cold and warm weather operation. This research aimed to understand the important mechanisms behind biological filtration methods in order to choose and optimize the best treatment strategy for full-scale testing and implementation. In doing so, a recommendation matrix was elaborated provided with the potential to be used as a universal operational strategy for wastewater treatment facilities located in environments of similar climate and ecology.

designing + (dis)assembling disputes: an ethnography of disputes & lawyers in the construction industry

The UK construction industry is notorious for the sheer amount of disputes which are likely to arise on each building and engineering project. Despite numerous creative attempts at “dispute avoidance” and “dispute resolution”, this industry is still plagued with these costly disputes. Whilst both academic literature and professional practices have investigated the causes of disputes and the mechanisms for avoidance/resolution of these disputes, neither has studied in any detail the nature of the construction disputes and why they develop as they do once a construction lawyer is engaged. Accordingly, this research explores the question of what influences the outcome of a construction dispute and to what extent do construction lawyers control or direct this outcome? The research approach was ethnographic. Fieldwork took place at a leading construction law firm in London over 18 months. The primary focus was participant observation in all of the firm’s activities. In addition, a database was compiled from the firm’s files and archives, thus providing information for quantitative analysis. The basis of the theoretical framework, and indeed the research method, was the Actor‐Network Theory (ANT). As such, this research viewed a dispute as a set of associations – an entity which takes form and acquires its attributes as a result of its relations with other entities. This viewpoint is aligned with relational contract theories, which in turn provides a unified platform for exploring the disputes. The research investigated the entities and events which appeared to influence the dispute’s identity, shape and outcome. With regard to a dispute’s trajectory, the research took as its starting point that a dispute follows the transformation of “naming, blaming, claiming…”, as identified by Felstiner, Abel and Sarat in 1980. The research found that construction disputes generally materialise and develop prior to any one of the parties approaching a lawyer. Once the lawyer is engaged, we see the reverse of the trajectory “naming, blaming, claiming…” this being: “claiming, blaming, naming…” The lawyers’ role is to identify or name (or rename) the dispute in the best possible light for their client in order to achieve the desired outcome – the development of which is akin to the design process. The transformation of a dispute and the reverse trajectory is by no means linear, but rather, iterative and spatial as it requires alliances, dependencies and contingencies to assemble and take the shape it does. The research concludes that construction disputes are rarely ever completely “resolved” as such. Whilst an independent third party may hand down a judgment, or the parties may reach a settlement agreement, this state is only temporal. Some construction disputes dissipate whist others reach a state of hibernation for a period of time only to pick up momentum and energy some years later. Accordingly, this research suggests that the concept of “dispute resolution” does not exist in the UK construction industry. The ultimate goal should be for parties to reach this ultimate and perpetual state of equilibrium as quickly and as cost effectively as possible: “dispute dissolution”, the slowing down of the dispute’s momentum. Rather than focusing on the design and assemblage of the dispute, the lawyers’ role therein is, or should be, to assist with the “disassembling” of the dispute.

Non-conventional advertising formats in television versus spots: An analysis based on the generated recall

Advertising investment and audience figures indicate that television continues to lead as a mass advertising medium. However, its effectiveness is questioned due to problems such as zapping, saturation and audience fragmentation. This has favoured the development of non-conventional advertising formats. This study provides empirical evidence for the theoretical development. This investigation analyzes the recall generated by four non-conventional advertising formats in a real environment: short programme (branded content), television sponsorship, internal and external telepromotion versus the more conventional spot. The methodology employed has integrated secondary data with primary data from computer assisted telephone interviewing (CATI) were performed ad-hoc on a sample of 2000 individuals, aged 16 to 65, representative of the total television audience. Our findings show that non-conventional advertising formats are more effective at a cognitive level, as they generate higher levels of both unaided and aided recall, in all analyzed formats when compared to the spot.