Adding Bricks to Clicks: The Contingencies Driving Cannibalization and Complementarity in Multichannel Retailing

This paper empirically explores the contingencies that drive cannibalizing and complementary effects across channels to provide sales forecasting, promotion planning, and customer relationship management guidance to multichannel managers. We investigate three contingencies in a sales analysis of a leading U.S. retailer who adds a new retail store channel to existing catalog and online channels. We show that the emergence and strength of cannibalizing and complementary effects varies over time, across type of channel, and by type of customer, and provide insight into when and where managers can expect these effects to dominate and how to counter cannibalization and promote complementarity across channels. We find that opening retail stores cannibalizes sales in the catalog and online channels in the short term, but produces complementary effects in both channels in the long term; cannibalization is magnified in the catalog channel, while complementarity is magnified in the online channel. Customer analysis suggests that opening retail stores paves the way for higher rates of customer acquisition and higher rates of repeat purchasing among existing customers in the direct channels in the long term.Multichannel Retailing, Channels of Distribution, Direct Marketing, E-commerce, Channel Management

ProxiMAX randomisation:a new technology for non-degenerate saturation mutagenesis of contiguous codons

Back in 2003, we published ‘MAX’ randomisation, a process of non-degenerate saturation mutagenesis using exactly 20 codons (one for each amino acid) or else any required subset of those 20 codons. ‘MAX’ randomisation saturates codons located in isolated positions within a protein, as might be required in enzyme engineering, or else on one face of an alpha-helix, as in zinc finger engineering. Since that time, we have been asked for an equivalent process that can saturate multiple, contiguous codons in a non-degenerate manner. We have now developed ‘ProxiMAX’ randomisation, which does just that: generating DNA cassettes for saturation mutagenesis without degeneracy or bias. Offering an alternative to trinucleotide phosphoramidite chemistry, ProxiMAX randomisation uses nothing more sophisticated than unmodified oligonucleotides and standard molecular biology reagents. Thus it requires no specialised chemistry, reagents nor equipment and simply relies on a process of saturation cycling comprising ligation, amplification and digestion for each cycle. The process can encode both unbiased representation of selected amino acids or else encode them in pre-defined ratios. Each saturated position can be defined independently of the others. We demonstrate accurate saturation of up to 11 contiguous codons. As such, ProxiMAX randomisation is particularly relevant to antibody engineering

Molecular basis of USP7 inhibition by selective small-molecule inhibitors

Ubiquitination controls the stability of most cellular proteins, and its deregulation contributes to human diseases including cancer. Deubiquitinases remove ubiquitin from proteins, and their inhibition can induce the degradation of selected proteins, potentially including otherwise 'undruggable' targets. For example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the tumour suppressor p53 in various cancers. Here we report that two compounds, FT671 and FT827, inhibit USP7 with high affinity and specificity in vitro and within human cells. Co-crystal structures reveal that both compounds target a dynamic pocket near the catalytic centre of the auto-inhibited apo form of USP7, which differs from other USP deubiquitinases. Consistent with USP7 target engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases levels of p53, and results in the transcription of p53 target genes, induction of the tumour suppressor p21, and inhibition of tumour growth in mice

BRICS: Ecological and Sustainability Implications of their Growth

This paper examines the environmental implications of the growing BRICS economies (Brazil, Russia, India, China and South Africa). Exploring the thesis that these economies will be bigger than the largest developed economies by 2050. The BRICS nations encompass more than 25% of the world\u92s land area, home to over 40% of the world\u92s population and have a combined GDP of over $20 trillion. The future growth of these economies significantly impacts the rest of the world. This Paper focuses in the growth and consumption patters of the continuing industrialized nations the implications it can have for the Environment. Alternative development models are pitted against the current capitalistic models of development to see which is a more suitable pick for the future

Stability of pore-plated membranes for hydrogen production in fluidized-bed membrane reactors

Pd-based membranes prepared by pore-plating technique have been investigated for the first time under fluidization conditions. A palladium thickness around 20 μm was achieved onto an oxidized porous stainless steel support. The stability of the membranes has been assessed for more than 1300 h in gas separation mode (no catalyst) and other additional 200 h to continuous fluidization conditions. Permeances in the order of 5·10−7 mol s−1 m−2 Pa−1 have been obtained for temperatures in a range between 375 and 500 °C. During fluidization, a small decrease in permeance is observed, as consequence of the increased external (bed-to-wall) mass transfer resistances. Moreover, water gas shift (WGS) reaction cases have been carried out in a fluidized bed membrane reactor. It has been confirmed that the selective H2 separation through the membranes resulted in CO conversions beyond the thermodynamic equilibrium (of conventional systems), showing the benefits of membrane reactors in chemical conversions