Perfect weddings abroad

Approximately 16% of UK couples are currently married abroad. However, academic or practitioner focused research that explores the complex nature of a couple’s buying preferences or the development of innovative marketing strategies by businesses operating within the weddings abroad niche sector, is almost non-existent. This exploratory paper examines the role and relevance of marketing within the weddings abroad sector. The complex nature of customer needs in this high emotional and involvement experience, are identified and explored. A case study of Perfect Weddings Abroad Ltd highlights distinctive features and characteristics. Social networking and the use of home-workers, with a focus on reassurance and handholding are important tools used to develop relationships with customers. These tools and techniques help increase the tangibility of a weddings abroad package. Clusters of complementary services that are synergistic and provide sources of competitive advantage are identified and an agenda for future research is developed

Work holding assessment of an UV adhesive and fixture design method

Adhesive work holding can be used to minimize clamping distortion and provide greater access to a work piece during machining. This paper proposes shear and tensile strength criteria to evaluate the work holding strength of adhesive grippers and definition of a strength safety coefficient of adhesive grippers. It also demonstrates a case study of work holding design with an UV adhesive for a grinding process based on a strength criteria explained in the paper. A test rig has been designed and manufactured to assess the capability of an adhesive work holding material. Tests include measurement of strength and repeatability of adhesion under different film thicknesses, curing times and pre-cleaning methods. The test shows the strength repeatability is less than ± 20%, which is good enough for many work holding applications. A shear-tensile combined strength can be evaluated by the strength sphere in a fixture design of a specific part geometry for production by the combined safety coefficient. Following the test rig assessment, a fixture has been designed with 3 grippers to demonstrate the adhesive for a grinding process with a simple part geometry. The method has a high potential for application in industry, and is not limited to the given part geometry and machining method. The grinding test shows that the adhesive work holding is strong enough for the application and that similar results can be expected for milling and turning with a good gripper arrangement

Convergence of marine megafauna movement patterns in coastal and open oceans

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 115 (2018): 3072-3077, doi:10.1073/pnas.1716137115.The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals’ movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyse a global dataset of 2.8 million locations from > 2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared to more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal micro-habitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise and declining oxygen content.Workshops funding granted by the UWA Oceans Institute, AIMS, and KAUST. AMMS was supported by an ARC Grant DE170100841 and an IOMRC (UWA, AIMS, CSIRO) fellowship; JPR by MEDC (FPU program, Spain); DWS by UK NERC and Save Our Seas Foundation; NQ by FCT (Portugal); MMCM by a CAPES fellowship (Ministry of Education)

FOXM1 binds directly to non-consensus sequences in the human genome.

BACKGROUND: The Forkhead (FKH) transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in most types of cancer. FOXM1, similar to other FKH factors, binds to a canonical FKH motif in vitro. However, genome-wide mapping studies in different cell lines have shown a lack of enrichment of the FKH motif, suggesting an alternative mode of chromatin recruitment. We have investigated the role of direct versus indirect DNA binding in FOXM1 recruitment by performing ChIP-seq with wild-type and DNA binding deficient FOXM1. RESULTS: An in vitro fluorescence polarization assay identified point mutations in the DNA binding domain of FOXM1 that inhibit binding to a FKH consensus sequence. Cell lines expressing either wild-type or DNA binding deficient GFP-tagged FOXM1 were used for genome-wide mapping studies comparing the distribution of the DNA binding deficient protein to the wild-type. This shows that interaction of the FOXM1 DNA binding domain with target DNA is essential for recruitment. Moreover, analysis of the protein interactome of wild-type versus DNA binding deficient FOXM1 shows that the reduced recruitment is not due to inhibition of protein-protein interactions. CONCLUSIONS: A functional DNA binding domain is essential for FOXM1 chromatin recruitment. Even in FOXM1 mutants with almost complete loss of binding, the protein-protein interactions and pattern of phosphorylation are largely unaffected. These results strongly support a model whereby FOXM1 is specifically recruited to chromatin through co-factor interactions by binding directly to non-canonical DNA sequences.We would like to acknowledge the Genomics and bioinformatics core at the CRUK Research Institute for the Illumina sequencing and the Proteomics core for the LC/MS-MS protein analysis for the RIME experiments. We acknowledge the support from The University of Cambridge and Cancer Research UK. The Balasubramanian Laboratory is supported by core funding from Cancer Research UK (C14303/A17197). SB is a Wellcome Trust Principle Investigator.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13059-015-0696-

Convergence of marine megafauna movement patterns in coastal and open oceans

The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals’ movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Replaced by a robot: Service implications in the age of the machine

Service organizations, emboldened by the imperative to innovate, are increasingly introducing robots to frontline service encounters. However, as they augment or substitute human employees with robots, they may struggle to convince a distrusting public of their brand’s ethical credentials. Consequently, this article develops and tests a holistic framework to ascertain a deeper understanding of customer perceptions of frontline service robots (FLSRs) than has previously been attempted. Our experimental studies investigate the effects of the (1) role (augmentation or substitution of human employees or no involvement) and (2) type (humanoid FLSR vs. self-service machine) of FLSRs under the following service contexts: (a) value creation model (asset-builder, service-provider) and (b) service type (experience, credence). By empirically establishing our framework, we highlight how customers’ personal characteristics (openness-to-change and preference for ethical/responsible service provider)  and cognitive evaluations (perceived innovativeness, perceived ethical/societal reputation, and perceived innovativeness-responsibility fit) influence the impact that FLSRs have on service experience and brand usage intent. Our findings operationalize and empirically support seminal frameworks from extant literature, as well as elaborate on the positive and negative implications of using robots to complement or replace service employees. Further, we consider managerial and policy implications for service in the age of machines

Causal theories, models and evidence in economics-some reflections from the natural sciences

Models have been extensively analysed in economic methodology, notably their degree of ability to provide explanations. This paper takes a complementary, comparative approach, examining theory development in the natural sciences. Examples show how diverse types of evidence combine with causal hypotheses to generate empirically based causal theories—a cumulative process occurring over a long timescale. Models are typically nested within this broader theory. This could be a good model for research in economics, providing a methodology that ensures good correspondence with the target system—especially as economics research is largely empirical, and has effective methods for causal inference. This paper analyses the key features of three successful theories in the natural sciences, and draws out some lessons that may be useful to economists. Some examples of good practice in economics are noted, e.g. involving money and banking, and the growth of the state. On the other hand, the widespread pre-crisis use of dynamic stochastic general equilibrium (DSGE) models that ignored the financial sector raises the question, how to realise what has been omitted? Nesting models in an empirically based causal theory could solve this. Furthermore, some phenomena have clear explanations, but mainstream theory obscures them, as with the Lucas puzzle about the direction of international capital flows. And, the prevailing theories about capitalist growth do not explain the basic evidence on its temporal and spatial distribution. Economics could beneficially learn from the natural sciences